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Existing biosimilars are safe, effective alternatives to their reference biologics, and are increasingly being incorporated into oncology treatment guidelines.

Technological advances that have emerged in the years since biologic agents entered the market allow for the careful assessment of “critical clinical attributes” of biosimilar agents. This helps ensure the safety and efficacy of biosimilars, as well as their structural, functional, and behavioral similarities to the original reference biologics, according to Gary Lyman MD, MPH, professor and senior lead, health care quality and policy at the Hutchinson Institute for Cancer Outcomes Research at Fred Hutchinson Cancer Research Center, Seattle.

Biosimilars are increasingly being included as acceptable alternatives in treatment guidelines, and in this episode Dr. Lyman discussed the reasons why they are considered safe and effective, how they can add value for oncology patients, and the need for ongoing diligence in monitoring their effects.

Biosimilars in oncology – key points:

The developers of biosimilar agents must prove biosimilarity to the reference agent, and generally go through “many of the same, if not all, preclinical steps.” Regulatory requirements are sufficient to ensure there are no clinically meaningful differences in the safety, purity, strength, and efficacy of biosimilars.
Unlike the originator biologics, biosimilars aren’t typically required to complete multiple costly phase 3 clinical studies that drive up drug costs. This has the potential to rein in drug prices for biologics, which have revolutionized oncology and many other fields – but at a significant price.
There has been some progress with respect to biologic cost reductions in the wake of biosimilar approvals, but the cost effects of biosimilars for newer reference agents will take time to emerge. Further prolonging the cost-reducing effects of biosimilar availability is the fact that early biosimilars were mainly used for supportive care whereas newer biosimilars are more often used for curative intent, which may lead to slower uptake due to hesitancy among clinicians and patients.
The European Medicines Agency (EMA) is about a decade ahead of the United States when it comes to approvals and acceptance of biosimilars. Of note, no approved biosimilar has been removed from the market due to concerns about safety and efficacy. This is “a huge testament to the durability of biosimilars and the strength of the regulatory process,” Dr. Lyman said, noting that the EMA and FDA have similar processes when it comes to such approvals.
“Drift,” the inevitable changes over time in an agent’s characteristics, can lead to changes in safety and efficacy. This means that diligence in monitoring effects and outcomes with both biologics and biosimilars is essential. Any concerns should be reported immediately and investigated.

Show notes written by Sharon Worcester, MA, a reporter for MDedge and Medscape.

Disclosures

Dr. Henry has no relevant disclosures. Dr. Lyman disclosed relationships with Amgen, Jazz Pharmaceuticals, Partners Therapeutics, Sandoz, Seattle Genetics, Bristol Myers Squibb, BeyondSpring, Samsung, G1 Therapeutics, and Merck.

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Systemic treatment for advanced urothelial cancer is quickly evolving. On this week’s podcast, Arjun Balar, MD, director of the genitourinary medical oncology program at New York University discusses his approach amid changing times with guest host Alan Lyss, MD, a community-based medical oncologist and clinical researcher in the St. Louis area before his recent retirement.

Chemotherapy or immunotherapy first line?

With the negative phase 3 results for chemotherapy in combination with either pembrolizumab or atezolizumab, “if I use immunotherapy, I use it alone,” Dr. Balar said.
Patients who need “a response right away” for aggressive disease get chemotherapy. In general, first-line chemotherapy “probably is the better route for a lot of people,” he said.
There is a role for immunotherapy in the first line when chemotherapy can’t be tolerated because of age or other reasons, and in the second line, immunotherapy is standard of care.
PD-1/PD-LI expression is too inconsistent to help guide the decision. It’s based instead on clinical judgement, given patient and disease characteristics.

Antibody-drug conjugates

The class includes enfortumab vedotin and sacituzumab govitecan, both approved for third-line treatment after chemo and immunotherapy.
Essentially, they are homing molecules targeting cancer-specific antigens coupled with a potent cytotoxic payload.
They have strong potential in combination with immunotherapy. “I think, in the next 3-5 years, we're going to find ADCs plus immunotherapy become the new standard of care,” Dr. Balar said.
New enfortumab vedotin data show activity in the second line among medically frail patients ineligible for chemotherapy who were treated instead with immunotherapy for metastatic disease. “This drug can potentially rescue those patients as an option after immunotherapy,” said Dr. Balar, an enfortumab vedotin investigator.

Next-generation sequencing

There’s no role yet for sequencing in the first line, but it’s necessary in later lines to check eligibility for drugs aimed at specific mutations, such as the tyrosine kinase inhibitor erdafitinib for patients with susceptible FGFR3 or FGFR2 genetic alterations.
Assays are available commercially from Foundation and other companies.
Results can take up to 6 weeks, so “I do it early on. I know that information is potentially going to be useful in making treatment decisions,” Dr. Balar said.

Enfortumabe vedotin adverse events

Side effects can include hyperglycemia within the first one or two cycles. Sometimes it’s asymptomatic, sometimes it’s accompanied by acid-base disturbances, and in very rare cases, it’s fatal. The problem is possibly linked to higher baseline body mass index.
At least half of patients develop a sunburn-like rash, also within the first one or two cycles, that spares the face and can be pruritic. It’s manageable by topical steroids, oral antihistamines, dose reductions, or dose interruptions.
“If anything severe is going to happen, it's going to happen within the first one or two cycles. I see [patients at] every visit” in the first two cycles “primarily to catch anything untoward,” Dr. Balar said.
Neuropathy is the “most significant dose-limiting toxicity, and tends to develop about 4 months into treatment,” he said.

Show notes written by M. Alexander Otto.

Dr. Balar disclosed research, advisory, and/or speaker relationships with Genentech, Incyte, Bristol-Myers Squibb, Janssen, Merck, Pfizer, AstraZeneca, and other companies. Dr. Lyss writes a column for MDedge Hematology/Oncology called “Clinical Insights” and had no other conflicts of interest.

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A “very basic” type of gene therapy could potentially cure hemophilia, but a major hurdle has been the lack of an effective mode of delivery. Recent strides in using adeno-associated virus (AAV) vectors are changing that, and Glenn Pierce, MD, World Federation of Hemophilia Vice President, Medical, predicts approvals in the next 12-18 months.

Dr. Pierce shared his personal experience with hemophilia and discussed his and others’ ongoing research on the use of AAV-mediated gene therapy with host David Henry, MD, in this episode.

Hemophilia and AAV gene therapy key points:

Hemophilia is caused by a monogenic defect and could, theoretically, be cured by gene replacement or augmentation, says Dr. Pierce, who notes that “it sounds disarmingly simple, but behind that simplicity is a very complex procedure.”
The approach uses “gene addition,” which is a basic gene therapy involving the addition of a normal gene to the variant in an individual. This ultimately corrects the clotting factor deficiency.
The complexity is in getting the normal gene into the body where it can have the intended therapeutic effect.
After more than 20 years of working to overcome that barrier, Dr. Pierce and others are finding success with using AAVs.
The approach has some similarities to that used in developing the mRNA COVID-19 vaccines but requires the use of DNA established within the virus (rather than mRNA) to provide a more stable effect. Questions about how long it will last are currently being investigated.
Multiple phase 3 trials are underway or completed. Data from two of those have been released in recent months, and the results are very encouraging: “It’s a remarkable achievement – many patients are doing well and, for all intents and purposes, could be considered free of [hemophilia],” Dr. Pierce says, adding that he would “potentially … use the ‘C word’ – cured – for at least a period of time.”
The therapy is generally well tolerated. Efforts are ongoing to identify the best ways to proactively and reactively use prednisone to manage side effects such as mild increases in transaminase levels.
To date, the risk-benefit profile appears reasonable for patients with clotting factor IX deficiency, and it is likely that the therapy in that setting “will march toward the regulatory process to determine if it’s safe and effective for approval,” he said.
Responses in those with clotting factor VIII deficiency have been more variable, with some patients requiring long-term prednisone use, which is problematic. More information is needed about this, but investigation is ongoing, he said.
Registries are available and many companies are involved in clinical trials. Clinicians and patients can look for information at clinicaltrials.gov, wfh.org (which publishes trial results and conducts workshops and meetings), and at the US National Hemophilia Foundation (Hemophilia.org) and the Society of Thrombosis and Hemostasis (ISTH.org).

Show notes written by Sharon Worcester, MA, a reporter for MDedge and Medscape.

Disclosures

Dr. Henry has no relevant disclosures. Dr. Pierce disclosed relationships with Ambys Medicines, BioMarin, BridgeBio, CRISPR Therapeutics, Decibel Therapeutics, Frontera, Geneception, Generation Bio, Novo Nordisk, Pfizer, Regeneron, Third Rock Ventures, Voyager Therapeutics, Global Blood Therapeutics, VarmX SAB, the National Hemophilia Foundation Medical and Scientific Advisory Council, and the World Federation of Hemophilia.

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At least 17 cases of thrombosis and thrombocytopenia have been reported in patients who received the Johnson & Johnson COVID-19 vaccine in the United States.

Such events have been reported in patients who received the AstraZeneca vaccine as well.

In this episode, Adam C. Cuker, MD, of the University of Pennsylvania, Philadelphia, tells host David H. Henry, MD, how to identify and manage patients with these vaccine-induced events.

What’s in a name?

The phenomenon of vaccine-induced thrombosis and thrombocytopenia has been given different names, including:
- Vaccine-induced immune thrombotic thrombocytopenia (VITT)
- Vaccine-induced prothrombotic immune thrombocytopenia (VIPIT)
- Thrombosis and thrombocytopenia syndrome (TTS).
Dr. Cuker’s preferred acronym is VITT.
VITT is an immune-mediated reaction to the Johnson & Johnson and AstraZeneca vaccines that “results in thrombocytopenia and a strong propensity for thrombosis,” Dr. Cuker explained.
Dr. Henry noted that VITT is reminiscent of heparin-induced thrombocytopenia (HIT).

Incidence unclear

VITT appears to be “very rare,” but “we still don't have a great sense of how common it is” because additional cases may not have been recognized or have yet to present, Dr. Cuker said.
VITT occurs about 5-30 days after vaccination.
VITT appears to be mediated by IgG antibodies, which take time to build up.
The exact mechanism is unknown, but VITT could be related to the adenovirus vector used in the Johnson & Johnson and AstraZeneca vaccines, Dr. Cuker said.
The first 15 cases of VITT associated with the Johnson & Johnson vaccine occurred in women, and most patients were aged under 50 years.
In Canada, where the AstraZeneca vaccine is available, cases of VITT have been reported in patients in their 80s and 90s.

Diagnosing VITT

Symptoms of VITT can include severe, unrelenting headache; severe abdominal pain; nausea and vomiting; as well as typical signs and symptoms of deep vein thrombosis or pulmonary embolism.
To determine if a patient has VITT, Dr. Cuker recommends ordering a disseminated intravascular coagulation panel – prothrombin time, partial thromboplastin time, fibrinogen, and D-dimer – as well as a standard HIT enzyme-linked immunosorbent assay (ELISA).
Rapid immunoassays for HIT are not reliable for VITT, so HIT ELISA must be used, Dr. Cuker emphasized.
Most patients with VITT have a “strongly positive” ELISA with optical density values “well in excess of 100 or 1.0,” depending on the scale, Dr. Cuker said.

Manage VITT like HIT

Patients should receive an anticoagulant, but not heparin, Dr. Cuker said. It isn’t clear if heparin will be harmful in patients with VITT, but current guidelines recommend avoiding heparin.
He also advised against using warfarin or vitamin K antagonists in patients with VITT “at least until their platelet count recovers.”
High-dose intravenous immunoglobulin (e.g., 1 g/kg for 2 consecutive days) is recommended, as it is believed to interfere with platelet activation.

Show notes written by M. Alexander Otto, a reporter for MDedge and Medscape.

DisclosuresDr. Henry has no relevant disclosures. Dr. Cuker has served as a consultant for Synergy Pharmaceuticals; has received authorship royalties from UpToDate; and his institution has received research support on his behalf from Alexion, Bayer, Novartis, Novo Nordisk, Pfizer, Sanofi, Spark Therapeutics, and Takeda.

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The combined clinical cell-cycle risk (CCR) score uses clinical and genetic factors to assess the risk of metastasis after radiation therapy in patients with prostate cancer.

The CCR score has proven accurate in studies and can guide post-radiation treatment decisions in practice, according to Jonathan D. Tward, MD, PhD, of the University of Utah, Salt Lake City.

Dr. Tward discusses the CCR score with host David Henry, MD, in this episode.

About the score

The CCR score combines the cell-cycle progression (CCP) score (available commercially as the Prolaris test) and the Cancer of the Prostate Risk Assessment (CAPRA) score to more precisely determine the postradiation risk for metastatic disease.
Investigators identified a threshold for determining precise risk levels (2.112), which allows for personalized treatment decision-making based on more individual characteristics than standard risk-group categorizations, according to Dr. Tward.
He noted that standard risk groups can include a broad range of actual risk even within a given category. Risk groups are “reasonably good at prognosticating who may or may not go on to have metastasis etc., but they’re not that good,” Dr. Tward said.

CCR score proves effective

Dr. Tward and colleagues evaluated the CCR score in a retrospective study published in Clinical Genitourinary Cancer (https://bit.ly/3vlgUwe).
The study included 718 men with intermediate- or high-risk localized prostate cancer who received single modality or multimodality therapy.
Results showed that patients with CCR scores below the identified threshold (2.112) could safely forgo multimodality therapy.

CCR score bests other scoring systems

In another study, the CCR score proved more accurate than other scoring systems.
Dr. Tward presented findings from this study at the 2021 Genitourinary Cancers Symposium (https://bit.ly/3eBvAjM).
The study included 741 men with intermediate- or high-risk localized prostate cancer who received single modality or multimodality therapy.
The CCR score predicted metastasis (hazard ratio, 2.21; C-index, 0.78) and did so better than National Comprehensive Cancer Network risk groups (C-index, 0.70), the CAPRA score alone (C-index, 0.71), or the CCP score alone (C-index, 0.69).
Dr. Tward said he has used the CCR score in his own practice for years and found it helpful.

Show notes written by Sharon Worcester, a reporter for MDedge and Medscape.

Disclosures

Both studies were funded by Myriad Genetics, the company that developed the Prolaris test. Dr. Tward disclosed relationships with Myriad Genetics and other companies. Dr. Henry has no relevant disclosures.

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Pediatric oncologists are used to dealing with emotional, heart-wrenching situations, but oncology took on a new dimension for Michael Weiner, MD, when both he and his daughter were diagnosed with cancer.

Dr. Weiner, a pediatric oncologist at Columbia University, New York, describes his roles as oncologist, patient, and caregiver to host David H. Henry, MD, in this episode.

Oncologist as patient: Lessons learned

Dr. Weiner’s journey as a cancer patient began when he felt a lymph node on his neck that he knew wasn’t “normal.”
A colleague examined Dr. Weiner and suggested the “watch-and-wait” approach, but Dr. Weiner insisted on immediate biopsy.
The diagnosis was follicular lymphoma, and Dr. Weiner had a hard time accepting that his malignancy was treatable but not curable.
One of the things Dr. Weiner learned as a cancer patient is that “you really need to connect with your doctor,” so he chose a doctor who felt like a good fit for him.
Another lesson Dr. Weiner learned was that cancer can be very isolating. Though friends and family can offer help and support, “you take this journey alone,” he said.
Dr. Weiner was treated with rituximab and radiation, which proved successful. It’s been 3 years since he completed his treatment.
Dr. Weiner had been reluctant to undergo radiation because of the risk of thyroid cancer, and, unfortunately, he now has a small thyroid nodule that’s under observation.
Update: After this episode was recorded, Dr. Weiner was diagnosed with papillary thyroid cancer. He is set to undergo a total thyroidectomy.

Oncologist as caregiver: Taking a backseat

Dr. Weiner’s daughter was diagnosed with papillary thyroid carcinoma after a nodule was found on a routine exam.
Dr. Weiner and his daughter decided to educate themselves about her malignancy and opted for an aggressive course of treatment.
“I tried very, very hard to be a parent and not a physician,” Dr. Weiner said.
He decided to put his faith in her care team. “I in no way participated in the final decision-making,” he said.
His daughter ultimately had a total thyroidectomy and high-dose radioactive iodine.
The process, like his own cancer journey, was difficult.

Dr. Weiner recounts these experiences in his book “Living Cancer: Stories from an Oncologist, Father, and Survivor,” which can be found here: https://bit.ly/3n7TB5Z.

Show notes written by M. Alexander Otto, a reporter for MDedge and Medscape.

Disclosures

Dr. Weiner and Dr. Henry have no relevant disclosures.

These show notes were updated on 4/22.

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Studies have shown that chimeric antigen receptor (CAR) T-cell therapies produce responses in patients with relapsed/refractory B-cell lymphomas, but researchers continue to look for ways to improve efficacy, decrease toxicity, and overcome treatment resistance.

Leslie Kean, MD, PhD, of Boston Children’s Hospital, discusses some of this research with host David H. Henry, MD, in this episode.

Dr. Kean outlines four recent studies of CAR T-cell therapies in lymphoma. The studies were selected as part of the “Best of ASH” session at the 2020 annual meeting of the American Society of Hematology.

Primary Analysis of ZUMA-5: A Phase 2 Study of Axicabtagene Ciloleucel (Axi-Cel) in Patients with Relapsed/Refractory Indolent Non-Hodgkin Lymphoma

This study was designed to assess the efficacy and safety of axicabtagene ciloleucel (axi-cel) in patients with indolent lymphomas.
In follicular lymphoma, the overall response rate (ORR) was 94%, and the complete response (CR) rate was 80%.
In marginal zone lymphoma, the ORR was 85%, and the CR rate was 60%.
There was one grade 5 and one grade 4 case of cytokine release syndrome (CRS).
Dr. Kean noted that 146 patients were evaluable for adverse events, so the single death related to CRS should be viewed in that context.
Overall, 82% of patients had CRS of any grade.
Jacobson C et al. ASH 2020, Abstract 700. https://bit.ly/32at91V.

What’s involved in a CAR T-cell study?

Dr. Kean explained that a patient is first deemed eligible by an oncologist and then enrolled in a CAR T-cell study.
For studies like ZUMA-5 that are testing autologous CAR T cells, basic lab work is done to ensure the patient has a high enough lymphocyte count.
The patient then undergoes apheresis, and the patient’s T cells are used to create the CAR T-cell product.
The company developing the product transduces the T cells with the CAR so the resulting CAR T cells will target cancer cells.
The therapy in ZUMA-5, axi-cel, targets CD19, which is expressed on B-cell lymphoma cells.
Normal B cells express CD19 as well, so immunoglobulin replacement is sometimes necessary to offset the loss of normal B cells.

Efficacy and Safety of Tisagenlecleucel in Adult Patients with Relapsed/Refractory Follicular Lymphoma: Interim Analysis of the Phase 2 ELARA Trial

Tisagenlecleucel differs from axi-cel in the signaling domain, though tisagenlecleucel targets CD19 as well, Dr. Kean explained.
She noted that tisagenlecleucel is a bit more long-lived than axi-cel.
In this trial, tisagenlecleucel produced an ORR of 82% and a CR rate of 65%.
There were no cases of grade 3 or higher CRS, which may be attributed to the different signaling domain, Dr. Kean said.
Fowler NH et al. ASH 2020, Abstract 1149. https://bit.ly/2OIGjjA.

TRANSCEND CLL 004: Phase 1 Cohort of Lisocabtagene Maraleucel (liso-cel) in Combination with Ibrutinib for Patients with Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)

Patients in this study received the CAR T-cell therapy liso-cel in combination with the BTK inhibitor ibrutinib.
The combination increased both efficacy and safety, as ibrutinib assisted in calming down the immune response.
There were no grade 5 adverse events and no cases of grade 4 CRS or neurotoxicity.
The ORR was 95%, and the CR rate was 63%.
There was no difference in response among patients who had or had not received a BTK inhibitor previously, Dr. Kean noted.
Wierda WG et al. ASH 2020, Abstract 544. https://bit.ly/3uPuJ5U.

CD58 Aberrations Limit Durable Responses to CD19 CAR in Large B Cell Lymphoma Patients Treated with Axicabtagene Ciloleucel But Can Be Overcome Through Novel CAR Engineering

Dr. Kean noted that CAR T-cell therapy typically produces a CR in more than 90% of patients within 30 days, but the long-term duration of response is about 50%.
With this study, researchers wanted to investigate why a CAR T-cell therapy would fail and determine if any tumor-specific factors affect the duration of response.
The team found that patients who had mutations in CD58 were less likely to achieve a CR to axi-cel, and most patients with these mutations ultimately progressed.
CD2, the T-cell ligand for CD58, plays adhesive and costimulatory roles in T cells, and CAR T cells rely on intrinsic T-cell signaling to work, Dr. Kean explained.
So if the CD2 in a CAR T cell can’t “see” CD58 on the tumor because of a mutation, the CAR T cell doesn’t work, she added.
To bypass this, the researchers created a construct integrating CD2 costimulatory domains within the CAR molecule so it expressed CD2 in a way that doesn’t require CD58.
The new construct “cures tumors like gangbusters” in mouse models, Dr. Kean said, adding that this CAR T-cell therapy could be coming to the clinic soon.
Maizner RG et al. ASH 2020, Abstract 556. https://bit.ly/3283zL0.

Looking ahead: Concerns about cost

Cost is a critical barrier to receiving CAR T-cell therapy, Dr. Kean noted, especially for patients who require additional treatment after receiving CAR T cells.
The next generation of CAR T-cell research should determine if this treatment is best used as a bridge to transplant or if CAR T-cell therapy can stand alone, she added.
To make the cost more palatable, CAR T-cell products should be a final cure, Dr. Kean said.

Show notes written by Malika Gill, MD, a resident at Pennsylvania Hospital, Philadelphia.

DisclosuresDr. Henry has no relevant disclosures. Dr. Kean disclosed relationships with Magenta Therapeutics, Bristol-Myers Squibb, Kymab, HiFiBiO Therapeutics, Regeneron, Novartis, Gilead, Bluebird Bio, and Forty Seven.

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Researchers have tracked the evolution of genetic germline testing in women with breast or ovarian cancer in recent years and reported the results in the Journal of Clinical Oncology.

Study author Allison W. Kurian, MD, of Stanford (Calif.) University, describes the group’s findings (https://bit.ly/31RaSGR) to guest host Alan Lyss, MD, subprincipal investigator emeritus for Heartland Cancer Research NCORP, in this episode.

Study rationale and methods

Dr. Kurian said that an inflection point for breast cancer genetics was in 2013 when the U.S. Supreme Court ruled that gene patenting was not allowed for the purposes of genetic testing. As a result, the cost of testing BRCA1/2 genes fell, and testing became much more accessible.
With their study, Dr. Kurian and colleagues aimed to look at trends following the increase in accessibility.
The researchers used Surveillance, Epidemiology, and End Results Program (SEER) records of women aged 20 years and older who were diagnosed with breast or ovarian cancer from 2013 to 2017 in California or Georgia. The team linked these data to results of clinical germline testing through 2019.
Dr. Kurian explained that the SEER data are comprehensive enough that all cancer cases in California and Georgia were likely included, the states provide a large catchment area of about 50 million people, and the states have different kinds of racial/ethnic diversity and urban/rural distribution.
The researchers used the data to assess testing trends as well as rates of variants of uncertain significance (VUS) and pathogenic variants (PVs).

Results by hypothesis

Hypothesis 1: Multigene panels will entirely replace testing for BRCA1/2 only.

This hypothesis was essentially correct. Testing of only two genes was almost totally replaced by testing many more genes.
The number of genes tested for breast cancer increased annually by 28% over the study period.

Hypothesis 2: Underutilization of testing patients with ovarian cancer will improve over time.

It is standard of care to recommend genetic testing for all ovarian cancer patients.
Based on 2013-2014 data, only one-third of women were tested.
As tests became more accessible in subsequent years, the hope was that more women would be tested.
Unfortunately, there was very little improvement in testing rates over the study period.

Hypothesis 3: More patients will be tested at lower levels of pretest risk for PVs.

In patients aged older than 60 years, testing rates increased for breast cancer (from 11% to 15%) and ovarian cancer (from 25% to 31%).
Patients aged younger than 45 years had lower testing rates over time, however.
Dr. Kurian noted that about 33% of ovarian cancer patients undergo genetic testing, but the goal is 100%.
It is unclear if the goal should be 100% for breast cancer, Dr. Kurian said.

Hypothesis 4: Sociodemographic difference in testing trends would not be seen.

There was not much of a gap observed with breast cancer patients. For example, among patients with breast cancer, approximately 31% of those who had genetic testing were uninsured, 31% had Medicaid, and 26% had private insurance or Medicare.
There is more of an equity issue with ovarian cancer. About 28% of those who had genetic testing were uninsured, 27% had Medicaid, and 39% had private insurance or Medicare.
Dr. Kurian said disparities in ovarian cancer persist in patients who are uninsured and those in certain racial/ethnic groups, including African Americans. These patients are less likely to get genetic testing.

Hypothesis 5: Detection of PVs and VUS will increase.

The detection of VUS increased at a higher rate in comparison with PVs when more genes were being tested. This is likely because of the fact that, for every PV you find, you will find many more VUS, Dr. Kurian said.

Hypothesis 6: Racial or ethnic disparities in rates of VUS will diminish over time.

Disparities actually increased over the study period as more genes were tested.
Some studies have suggested that VUS results lead to unnecessary prophylactic surgery, Dr. Kurian said. She added that the decision to undergo prophylactic surgery should not be based on a VUS because “the great majority of VUS turn out to be nothing.”

Additional findings and implications for practice

The study revealed that most PVs were in 20 genes associated with breast or ovarian cancer.
Dr. Kurian and colleagues concluded that the way to improve testing is to focus on those 20 genes and ensure appropriate patients are being tested, rather than adding more genes to tests.
Dr. Kurian said it is urgent to increase genetic testing in patients with ovarian cancer, as it is not being done at the rate it should be.
Dr. Kurian also noted that one positive outcome of the COVID-19 pandemic has been an increase in telehealth visits and at-home genetic testing.
Providing patients with these more convenient options could increase the use of genetic testing.

Show notes written by Alesha Levenson, MD, a resident at Penn Medicine, Philadelphia.

Disclosures

Dr. Kurian disclosed relationships with Myriad Genetics, Ambry Genetics, Color Genomics, GeneDx/BioReference, InVitae, and Genentech. The study was supported by the National Cancer Institute, the Centers for Disease Control and Prevention, and the California Department of Public Health.

Dr. Lyss writes a column for MDedge Hematology/Oncology called “Clinical Insights” (https://bit.ly/3m76xIP). He has no other conflicts of interest.

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A program called Drive By Flu-FIT has allowed for socially distanced colorectal cancer (CRC) screening during the COVID-19 pandemic.

Armenta Washington, senior research coordinator at the University of Pennsylvania, describes the program to guest host Alan Lyss, MD, subprincipal investigator emeritus for Heartland Cancer Research NCORP, in this episode.

What is Drive By Flu-FIT?

Drive By Flu-FIT is a socially distanced version of the Flu-Fecal Immunochemical Test (Flu-FIT) program.
Flu-FIT was designed to increase access to CRC screening by offering take-home FIT tests to patients at the time of their annual flu shots.
The goal of Drive By Flu-FIT is to provide a COVID-safe approach to CRC screening and counteract the decrease in CRC screening seen during the pandemic.
Drive By Flu-FIT is a joint effort of the University of Pennsylvania, the Einstein Healthcare Network, Chi Eta Phi Sorority, and Enon Tabernacle Baptist Church, the largest Baptist church in the Philadelphia region.

How does Drive By Flu-FIT work?

To participate in a Drive By Flu-FIT event, community members had to complete eligibility, registration, and demographic questionnaires online.
Patients who were enrolled watched a short educational video on CRC and completed two questionnaires – one on CRC screening knowledge (14 items) and one on screening intentions (5 items) – before and after watching the video.
At the Drive By Flu-FIT events, patients remained in their cars while physicians in personal protective equipment handed out FITs and explained how to use them and return them.
Patients could also receive a flu vaccine at each event.

Results: High return rate

According to initial data, 335 patients registered for a Drive By Flu-FIT event, but 80 (23.9%) ultimately didn’t attend and 63 (18.8%) were found to be ineligible.
A total of 192 patients attended and received a FIT (57.3%).
Scores on both questionnaires increased after patients watched the educational video.
Patients’ baseline knowledge of CRC was high but lacking in four areas: risk factors for CRC, the optimal frequency of FITs, the link between Lynch syndrome and CRC, and the relationship between physical activity and CRC risk.
Of the 192 patients who received a FIT, 38 (19.7%) did not return it.
There were 141 patients (73.4%) with a negative FIT result, while 13 (6.7%) had a positive FIT result and were referred for colonoscopy.

Resources

For more information on Flu-FIT, visit http://flufit.org/.
For more details on Drive By Flu-FIT, see:
- AACR Virtual Meeting: COVID-19 and Cancer, Abstract S02-04: https://bit.ly/3szf0Hp.
- MDedge coverage of the meeting presentation: https://bit.ly/3szfrl1.

Ms. Washington disclosed no conflicts of interest. The study was supported by the National Cancer Institute. The FITs were donated by Polymedco, and the flu vaccines were donated by the Philadelphia Public Health Department.

Dr. Lyss writes a column for MDedge Hematology/Oncology called “Clinical Insights” (https://bit.ly/3m76xIP). He has no other conflicts of interest.

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Earlier this year, clinical practice guidelines for the diagnosis and management of von Willebrand disease (VWD) were published in Blood Advances.

The guidelines (https://bit.ly/2OIfKLE) are a collaborative effort from the American Society of Hematology, the International Society on Thrombosis and Haemostasis, the National Hemophilia Foundation, and the World Federation of Hemophilia.

Guideline author Paula James, MD, of Queens University, Kingston, Ont., reviews some of the recommendations in these guidelines with host David H. Henry, MD, in this episode.

Case discussion

A patient presents with the complaint of heavy menstrual bleeding, which could indicate a bleeding disorder such as VWD. How does one diagnose or rule out VWD?

Tests to order include CBC, prothrombin time (PT), and partial thromboplastin time (PTT).
Results of CBC, PT, and PTT could be normal, which would necessitate special testing to specifically look at factor VIII and von Willebrand factor (VWF).
A patient’s family history may be helpful, as most types of VWD are autosomal dominant, though two subtypes are recessive.

Diagnostic evaluation of VWD

VWF is the chaperone protein for factor VIII in the intrinsic pathway, which is measured by the PTT.
In more severe forms of VWD, the PTT is prolonged because of factor VIII.
VWF is measured separately because it is not reflected in the PT or PTT.
The recommendation is to measure VWF antigen and employ a functional assay to see how well VWF binds platelets.
- The recommendation in the new guidelines is to use the GPIbM assay rather than the ristocetin cofactor assay.
  - Many labs in the United States are still using the ristocetin cofactor assay. However, in Canada, Europe, and other parts of the world, many labs have moved to a newer assay that is automated. It has a much lower coefficient of variation and fewer issues with measurement of VWF in Black populations, which is a major issue with the cofactor assay.

Types of VWD

Type 1 VWD is characterized by a decreased amount of VWF.
- Type 1 patients have low VWF antigen and low platelet-dependent VWF function to a similar degree, with low or normal factor VIII.
Type 2 VWD is characterized by aberrant VWF.
- The functional assay is a lot lower than VWF antigen.
- The platelet-dependent function to VWF antigen ratio cutoff is 0.7.
- Further testing is warranted to determine subtypes (2A, 2B, 2N, or 2M), including VWF multimers. Genetic testing can be helpful to further delineate subtypes.
Type 3 VWD is characterized by the absence of VWF.
- The patient will have a VWF antigen level of 0, platelet-dependent VWF function of 0, and a reduced factor VIII level (usually less than 10%).

Pregnant patients with VWD

There is a protective adaptation in pregnancy, in which factors normalize in the third trimester, which works to prevent hemorrhage at delivery.
This protective effect is because of the hormonal changes of pregnancy, and it is seen in patients with milder forms of VWD.
WVF levels peak within 8-24 hours after delivery and then slowly return to baseline.
There is a risk of delayed postpartum hemorrhage once VWF levels return to baseline, which tends to happen 7-14 days postpartum.

Procedural planning: Desmopressin challenge test

Desmopressin causes the release of VWF from the Weibel-Palade bodies of the endothelium, and it can be used as prophylaxis or treatment of bleeding in type 1 VWD.
The desmopressin challenge test is used to check how the patient responds to desmopressin when well, to predict the patient’s response after an anticipated procedure.
The test involves measuring VWF levels before desmopressin is given and at 1 hour, 2 hours, and 4 hours after desmopressin administration.
The idea is to measure the magnitude of increase in VWF levels and observe how sustained that increase is to predict the patient’s response to desmopressin after future procedures.
There is a subset of patients with type 1 VWD who have increased clearance of VWF that causes their decreased VWF levels. They may not have a sustained plateau in the VWF level after desmopressin, which emphasizes why testing as far as 4 hours after desmopressin administration is important.
The dose of desmopressin given in this test is typically 0.3-0.4 mcg/kg.

Recommendations for preprocedure prophylaxis for type 1 VWD

Minor procedures (e.g., wisdom tooth extraction)
- The patient should receive an antifibrinolytic agent, such as tranexamic acid or aminocaproic acid, 2 hours before the procedure, followed by desmopressin 30-60 minutes prior to the procedure.
- After the procedure, the patient should continue to receive the antifibrinolytic agent for 3-4 days.
Major procedures/surgeries (e.g., gallbladder removal)
- The guidelines do not recommend desmopressin for major procedures because patients need to be fluid-restricted for approximately 24 hours after administration because of the risk of hyponatremia.
  - Desmopressin is a synthetic analog of vasopressin, which results in the accumulation of free water similarly to vasopressin.
- The guidelines do recommend giving VWF-containing concentrate to increase VWF and factor VIII to greater than 50% from baseline for at least 3 days.
- VWF concentrates can be given every 12 hours or as continuous intravenous infusions.
- Tranexamic acid should be given as an adjuvant both prior to the procedure and in the days following.
- Cryoprecipitate is not recommended because it can’t be virally inactivated.

Preprocedure prophylaxis in type 2 or 3 VWD

Desmopressin does not work for most patients with type 2 or 3 VWD. So even for minor procedures, these patients will need to receive VWF concentrate coupled with antifibrinolytics.

Show notes written by Sheila DeYoung, DO, a resident at Pennsylvania Hospital, Philadelphia.

Disclosures

Dr. Henry has no relevant disclosures. Dr. James disclosed relationships with Baxter/Baxalta/Shire, CSL Behring, Bayer, and Octapharma.

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We continue our review of drugs recently approved by the Food and Drug Administration (FDA) in the hematology/oncology space.

In part 1 of our review, David M. Mintzer, MD, of Pennsylvania Hospital, highlighted 11 therapies, including newly-approved treatments and new indications for older drugs. Part 1 was published Feb. 18 (https://bit.ly/38JR782).

Now, in part 2, Dr. Mintzer tells host David H. Henry, MD, about another 11 therapies recently approved by the FDA, including monoclonal antibodies, kinase inhibitors, chimeric antigen receptor (CAR) T-cell therapies, and more.

Margetuximab-cmkb (Margenza)

In Dec. 2020, margetuximab-cmkb was approved for use in combination with chemotherapy to treat adults with metastatic, HER2-positive breast cancer who had received at least two prior anti-HER2 regimens, including at least one for metastatic disease. https://bit.ly/38JAiKg

Tafasitamab-cxix (Monjuvi)

In July 2020, tafasitamab-cxix received accelerated approval for use in combination with lenalidomide to treat adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, including DLBCL arising from low-grade lymphoma, who are not eligible for autologous stem cell transplant. https://bit.ly/3vtiHQF

Lurbinectedin (Zepzelca)

In June 2020, lurbinectedin received accelerated approval to treat adults with metastatic small-cell lung cancer with disease progression on or after platinum-based chemotherapy. https://bit.ly/30KcnpB

Belantamab mafodotin-blmf (Blenrep)

In Aug. 2020, belantamab mafodotin-blmf received accelerated approval to treat adults with relapsed or refractory multiple myeloma who had received at least four prior therapies, including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent. https://bit.ly/3lkPLWd

Umbralisib (Ukoniq)

In Feb. 2021, the FDA granted umbralisib accelerated approval to treat adults with relapsed or refractory marginal zone lymphoma who had received at least one prior anti-CD20-based regimen and adults with relapsed or refractory follicular lymphoma who had received at least three prior lines of systemic therapy. https://bit.ly/3bQqtMM

Azacitidine tablets (Onureg)

In Sept. 2020, the FDA approved azacitidine tablets for continued treatment of patients with acute myeloid leukemia who had achieved a first complete remission or complete remission with incomplete blood count recovery after intensive induction chemotherapy and who are not able to complete intensive curative therapy. https://bit.ly/38KFT2Z

Decitabine and cedazuridine tablets (Inqovi)

In July 2020, the FDA approved an oral combination of decitabine and cedazuridine to treat adults with myelodysplastic syndromes (MDS). This includes previously treated and untreated, de novo and secondary MDS (including refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, and chronic myelomonocytic leukemia), as well as intermediate-1, intermediate-2, and high-risk MDS. https://bit.ly/3lmqlI4

Tepotinib (Tepmetko)

In Feb. 2021, the FDA granted accelerated approval to tepotinib for adults with metastatic non-small cell lung cancer (NSCLC) harboring MET exon 14 skipping alterations. https://bit.ly/3lmqBXy

Pralsetinib (Gavreto)

In Sept. 2020, pralsetinib received accelerated approval to treat adults with metastatic RET fusion-positive NSCLC. https://bit.ly/3vrS26I

In Dec. 2020, the FDA granted full approval to pralsetinib to treat adult and pediatric patients ages 12 and older with advanced or metastatic RET-mutant medullary thyroid cancer who require systemic therapy or those with RET fusion-positive thyroid cancer who require systemic therapy and are refractory to radioactive iodine. https://bit.ly/3eCVXrs

Brexucabtagene autoleucel (Tecartus)

In July 2020, the FDA granted accelerated approval to brexucabtagene autoleucel, a CD19-directed CAR T-cell therapy, for the treatment of adults with relapsed or refractory mantle cell lymphoma. https://bit.ly/3tBtqH9

Lisocabtagene maraleucel (Breyanzi)

In Feb. 2021, another CD19-directed CAR T-cell therapy, lisocabtagene maraleucel, was approved to treat adults with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy. The approval encompasses DLBCL not otherwise specified (including DLBCL arising from indolent lymphoma), high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B. https://bit.ly/3lljHBx

Disclosures

Dr. Mintzer and Dr. Henry have no relevant disclosures.

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Treatments for chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL) have advanced in recent years, with more new developments on the horizon.

James Gerson, MD, of the University of Pennsylvania, Philadelphia, reviewed some of these advances and future directions while describing how he would treat three patients. Host David H. Henry, MD, posed the following cases for consideration.

Case 1

In a 75-year-old male with no comorbid illness, routine blood work revealed a WBC count of 15,000/mcL. The manual differential showed mature lymphocytes and smudge cells. The patient has no constitutional symptoms, but there is suspicion of CLL. What to do?

An incidental finding of elevated WBC is the most common presentation for CLL, Dr. Gerson noted.
Flow cytometry is how most diagnoses are made. If the patient’s blood sample is CD5+ and CD20+, in the vast majority of cases, the patient has CLL.
The main alternative diagnosis is MCL, so Dr. Gerson recommends checking for cyclin-D1 overexpression and translocation (11;14), which would be present in MCL.
Dr. Gerson also recommends fluorescence in situ hybridization (FISH), cytogenetics, and next-generation sequencing to assist with prognostication.
When the exam is normal and the patient is asymptomatic, no imaging is required.
For this patient, treatment should be deferred until disease progression.

Case 2

A 75-year-old, fit male has a WBC of 25,000/mcL, noted after the patient reported not feeling well, having a distended abdomen, night sweats, and weight loss. Blood work shows a hemoglobin level of 10.5 g/dL and a platelet count of 130 x 103/mcL. What to do?

Because this patient is symptomatic, treatment is indicated, Dr. Gerson said.
However, because of the pandemic, Dr. Gerson would likely delay therapy, perhaps until after COVID-19 vaccination.
To assess risk, Dr. Gerson would perform immunohistochemistry, FISH, and next-generation sequencing in this patient.
Patients with 17p deletion have high-risk disease, those with TP53 missense or nonsense mutations have even higher-risk disease, and patients with both a deletion and a mutation are “at excessively high risk,” Dr. Gerson said.
He favors giving a BTK inhibitor to patients with TP53 mutation/17p deletion because of results from the CLL14 trial (N Engl J Med 2019; 380:2225-36. https://bit.ly/38pVHbf).
However, because of the “small signal” in the trial, Dr. Gerson said plenty of his colleagues use a BTK inhibitor interchangeably with a BCL2 inhibitor and anti-CD20 therapy (e.g., venetoclax and obinutuzumab).
Dr. Gerson said ibrutinib and acalabrutinib have similar efficacy, according to unpublished results of the ELEVATE-RR trial (https://bit.ly/38onIjy).
Both drugs inhibit platelets, and there appears to be a higher risk of atrial fibrillation with ibrutinib.

Case 3

A 75-year-old, fit male has an elevated WBC, noted after complaints of bone pain, weight loss, night sweats, and enlarged lymph nodes. There is suspicion of MCL. What to do?

MCL is a complicated disease and “incredibly” heterogeneous in clinical and pathological behavior, Dr. Gerson noted.
The classic finding in MCL is cyclin-D1 overexpression caused by (11;14) translocation, but there are atypical translocations as well.
The approach to first-line treatment of MCL varies and may include cytarabine-based induction, bendamustine plus rituximab, or rituximab alone.
Brexucabtagene autoleucel, a chimeric antigen receptor T-cell therapy, is changing the landscape of treatment for relapsed/refractory MCL, Dr. Gerson said, as this treatment may offer a cure.
Investigational therapies for MCL include the BTK inhibitor pirtobrutinib (LOXO-305) and hematopoietic stem cell transplant.
Pirtobrutinib is under investigation in patients with MCL, CLL, and other indolent lymphomas that have progressed on or are intolerant to first-line therapy (Lancet. 2021 Mar 6;397[10277]:892-901. https://bit.ly/3rvRv1h).

Show notes written by Ronak Mistry, DO, a resident at Pennsylvania Hospital, Philadelphia.

Disclosures

Dr. Gerson disclosed relationships with Loxo Oncology, Genentech, Pharmacyclics, and TG Therapeutics. Dr. Henry has no relevant disclosures.

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When should cancer patients receive a COVID-19 vaccine? The National Comprehensive Cancer Network (NCCN) has issued recommendations to provide guidance on the topic.

Guideline author Steven Pergam, MD, of Fred Hutchinson Cancer Research Center, Seattle, explains NCCN’s recommendations to host David H. Henry, MD, in this episode.

Prioritization

Prioritization for COVID-19 vaccination should be given to cancer patients currently receiving chemotherapy, those who just finished active treatment, or those about to receive treatment.
Additional factors that should be taken into consideration include age, comorbidities, and sociodemographic characteristics.

Transplant and cellular therapy

Patients who undergo allogeneic or autologous transplant or those who receive cellular therapy should be vaccinated at least 3 months after this treatment.
This recommendation is based on best practices used for other vaccines, as there are insufficient data on COVID-19 vaccination in these patients, Dr. Pergam noted.

Hematologic malignancies

For patients with hematologic malignancies receiving intensive cytotoxic chemotherapy, vaccination should be delayed until absolute neutrophil count recovery.
Patients with marrow failure from disease, those receiving therapy expected to have limited or no recovery, and those on long-term maintenance therapy should get vaccinated when a vaccine is available to them.

Antibody response

There are no current data to support checking antibodies prior to vaccination, as one will lose antibodies over time, Dr. Pergam noted.
Likewise, there are no data to support testing for antibodies after vaccination.

Solid tumor malignancies

Patients with solid tumor malignancies who are receiving cytotoxic chemotherapy, targeted therapy, radiation, or checkpoint inhibitors or other immunotherapies should be vaccinated when a vaccine is available to them.
For patients undergoing surgery, there should be adequate time between receiving a vaccine and the surgical date, as side effects from the vaccine, such as fever, can delay surgery.

These guidelines are available for download from the NCCN website: https://www.nccn.org/covid-19/.

Show notes written by Malika Gill, MD, a resident at Pennsylvania Hospital, Philadelphia.

Disclosures

Dr. Pergam and Dr. Henry have no relevant disclosures.

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Ifeyinwa (Ify) Osunkwo, MD, MPH, joins us to talk about her approach to pain management in patients suffering from sickle cell crisis as well as the cognitive and behavioral effects of long-term opioid use in these patients. She and our host David H. Henry, MD, cover these topics and more in this episode.

Dr. Osunkwo is a professor of medicine at Atrium Health and the director of the Sickle Cell Enterprise at the Levine Cancer Institute, part of Atrium Health, in Charlotte, N.C.

Over the course of a decade, the life expectancy of patients with sickle cell disease has increased.
Today 99% of children with sickle cell disease will live to become adults.
When treating patients with sickle cell pain it is important to consider their disease trajectory, and to weigh the pros and cons for initiation of opioid therapy.

Management of sickle cell disease in the acute setting:

In children, therapy usually includes use of intravenous fluid and intravenous opioids, then an eventual transition to oral opioids and NSAIDS.
In adolescents, exposure to a prolonged course of high-dose opioids actually has been shown to exacerbate their pain.
PCA (patient-controlled analgesia) versus “PRN” or as-needed medications removes the dependency on the external environment to receive pain medications and lessens the degree of psychological stress in these patients.
Use of intravenous ketamine as an adjuvant to opioids in patients with an acute exacerbation has been shown to improve outcomes in patients (i.e., better pain control, decreased hospital stay, and management of anxiety and stress of a pain crisis.)
In the acute pain setting, it is important to go through all differentials to get to where you are treating the right cause of pain.
Following hospitalization, these patients often present back to the hospital in subacute opioid withdrawal. The key here is to engage patients in long term treatment plans.
For opioid-induced itching, it has been shown that in patients who receive intravenous Benadryl have worse outcomes than in patients that receive oral Benadryl.

Long-term side effects of chronic opioid therapy use:

Psychological and behavioral side effects including insomnia, reduced libido, tolerance, oppositional behavior, poor memory, psychosis, paranoia, increased depression/anxiety and confusion.
The opioid risk score is a helpful screening test that looks at the risk of adverse opioid outcomes. Specifically, family history of substance abuse, personal history of substance abuse, history of person abuse or psychological diagnosis results in a higher score which correlates with a higher risk of negative outcomes.
Use of suboxone has proved to be very beneficial in patients on chronic opioid therapy in preventing frequent hospitalizations.

Show notes written by Alesha Levenson, MD, a resident with Penn Medicine, Philadelphia.

Disclosures

Dr. Osunkwo disclosed relationships with Terumo, Global Blood Therapeutics, Acceleron, FORMA Therapeutics, Health Resources and Services Administration, Patient Centered Outcomes Research Institute, Micella Biopharma, Pfizer, and Novartis. Dr. Henry has no relevant disclosures.

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In this episode, we review drugs recently approved by the Food and Drug Administration in the hematology/oncology space.

David M. Mintzer, MD, of Pennsylvania Hospital, joins host David H. Henry, MD, to highlight some first-time approvals and new indications for older drugs.

Approvals in 2020Pembrolizumab (Keytruda) was approved for a range of new indications last year, including:

First-line treatment of patients with unresectable or metastatic microsatellite instability–high or mismatch repair deficient colorectal cancer. https://bit.ly/2OKw8uF.
Treatment of adult and pediatric patients who have tumor mutational burden–high (≥10 mutations/megabase) solid tumors that progressed after prior treatment and who have no satisfactory alternative treatment options. https://bit.ly/2NCddkX.
For use in combination with chemotherapy for the treatment of patients with locally recurrent unresectable or metastatic triple-negative breast cancer whose tumors express PD-L1 (combined positive score ≥10) as determined by an FDA-approved test. https://bit.ly/2ZobcMc.
To treat patients with recurrent or metastatic cutaneous squamous cell carcinoma that is not curable by surgery or radiation. https://bit.ly/3ashYGV.

Avelumab (Bavencio) was approved for maintenance therapy in patients with locally advanced or metastatic urothelial carcinoma that has not progressed with first-line platinum-containing chemotherapy. https://bit.ly/3ar8XOs.

Nivolumab (Opdivo) was approved for:

Patients with unresectable advanced, recurrent, or metastatic esophageal squamous cell carcinoma after prior fluoropyrimidine- and platinum-based chemotherapy. https://bit.ly/3ar4bjX.
Use in combination with ipilimumab as first-line treatment in adults with unresectable malignant pleural mesothelioma. https://bit.ly/2NbQ60V.

Atezolizumab (Tecentriq) was approved in combination with cobimetinib and vemurafenib for patients with BRAF V600 mutation-positive unresectable or metastatic melanoma. https://bit.ly/2NzkodG.

Osimertinib (Tagrisso) was approved for adjuvant therapy after tumor resection in patients with non–small cell lung cancer whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test. https://bit.ly/2NC0aQs.

Selinexor (Xpovio) was approved for:

Use in combination with bortezomib and dexamethasone for the treatment of adults with multiple myeloma who have received at least one prior therapy. https://bit.ly/3s1u1kp.
Adults with relapsed or refractory diffuse large B-cell lymphoma not otherwise specified, including disease arising from follicular lymphoma, after at least two lines of systemic therapy. https://bit.ly/2M172GW.

The FDA also approved a new fixed-dose combination of pertuzumab, trastuzumab, and hyaluronidase-zzxf (Phesgo) for subcutaneous injection for:

Use in combination with chemotherapy as neoadjuvant treatment of patients with HER2-positive, locally advanced, inflammatory, or early-stage breast cancer (either greater than 2 cm in diameter or node positive) as part of a complete treatment regimen for early breast cancer.
Use in combination with chemotherapy as adjuvant treatment of patients with HER2-positive early breast cancer at high risk of recurrence.
Use in combination with docetaxel to treat patients with HER2-positive metastatic breast cancer who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease. https://bit.ly/2LXA4XX.

Relugolix (Orgovyx) was the first oral gonadotropin-releasing hormone receptor antagonist approved by the FDA for adults with advanced prostate cancer. https://bit.ly/3qyJisQ.

Approvals in 2021

Cemiplimab-rwlc (Libtayo) was approved for patients with locally advanced or metastatic basal cell carcinoma previously treated with a hedgehog pathway inhibitor or for whom a hedgehog pathway inhibitor is not appropriate. https://bit.ly/3ppkW31.

Daratumumab plus hyaluronidase (Darzalex Faspro) was approved in combination with bortezomib, cyclophosphamide, and dexamethasone for newly diagnosed light chain amyloidosis. https://bit.ly/3bbaF5I.

Approval in 2019

In late 2019, the FDA approved fam-trastuzumab deruxtecan-nxki (Enhertu) for patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting. https://bit.ly/3qw9tA4.

Show notes written by Sheila DeYoung, DO, a resident at Pennsylvania Hospital, Philadelphia.

Disclosures

Dr. Mintzer and Dr. Henry have no relevant disclosures.

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The NCI-MATCH trial was designed to reveal mutations in underexplored cancer types, allowing researchers to match patients to appropriate targeted therapies.

Study investigator Alice P. Chen, MD, from the National Cancer Institute, reviews the goals and results of NCI-MATCH with host David H. Henry, MD, in this episode.

Trial details

NCI-MATCH has more than 1,000 participating sites.
The trial is open to patients with advanced cancers that have progressed on standard treatment or rare cancers for which there is no standard treatment.
Investigators use next-generation sequencing to identify mutations in tumor biopsies taken before the start of therapy.
Sequencing is performed at MD Anderson Cancer Center, Houston; Massachusetts General Hospital, Boston; MoCha at NCI’s Frederick (Md.) National Lab; Yale University, New Haven, Conn.; and commercial labs.

Matching patients to treatment

When a patient is found to have an actionable mutation, that patient is assigned to an investigational treatment, typically monotherapy.
A patient cannot be assigned to a treatment that is already known to be effective against their cancer; for example, patients with BRAF-mutated melanoma were excluded.
The NCI’s Cancer Therapy Evaluation Program sends the patient's targeted therapy to the participating site within 24 hours of notification.
CT imaging is done prior to the start of treatment, and patients are monitored with repeat scans every two cycles.

Results

Data on 5,954 patients with refractory malignancies were recently reported (J Clin Oncol. 2020 Nov 20;38[33]:3883-94).
About 38% of those patients had an actionable mutation, and about 18% were assigned to a targeted therapy.
Reports have shown varying response rates to matched therapy, ranging from 2% to 38%, Dr. Chen said.
Results from the trial's treatment arms can be found here: https://ecog-acrin.org/nci-match-eay131-findings.
Dr. Chen noted that this trial was designed to match patients with single agents.
Combination therapy has only been used in one arm of the study (J Clin Oncol. 2020 Aug 06. doi: 10.1200/JCO.20.00762).

Future directions

Nine treatment arms are still open, and one arm has yet to open.
Conclusions are still pending the completion of the treatment arms.
The next step for this research is expanding to include more combination therapies.
There is also interest in comparing biopsies of tissue obtained at initial diagnosis and after treatment to further improve understanding of mutations.
For more information on NCI-MATCH, visit:
- https://www.cancer.gov/about-cancer/treatment/clinical-trials/nci-supported/nci-match.
- https://www.cancer.gov/about-cancer/treatment/clinical-trials/search/v?id=NCT02465060.

Show notes written by Sheila DeYoung, DO, a resident at Pennsylvania Hospital, Philadelphia.

Disclosures

Dr. Chen and Dr. Henry have no conflicts of interest.

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How do the various COVID-19 vaccines work, and when should patients be vaccinated? We tackle these topics and more in this episode.

Our host David H. Henry, MD, is joined by Drew Weissman, MD, PhD, a professor at the University of Pennsylvania, Philadelphia. Dr. Weissman codeveloped the messenger RNA (mRNA) technology being used in the COVID-19 vaccines produced by Pfizer/BioNTech and Moderna.

History of mRNA vaccines

Testing of mRNA vaccines began in the 1990s.
An initial problem with these vaccines was that the RNA was highly inflammatory.
Dr. Weissman and his colleague, Katalin Karikó, PhD, discovered how to fix that problem in 2005.
The pair found that placing modified nucleosides into mRNA made it noninflammatory and allowed for increased production of protein from the RNA – up to a 1,000-fold increase in mice.
This technology is the basis of the Moderna and Pfizer/BioNTech COVID-19 vaccines.

Immunology and vaccines

To produce a good immune response, antigen must be present for a long time, though the optimal amount of time is unknown, Dr. Weissman said.
The mRNA lipid nanoparticles (LNPs) used in the COVID-19 vaccines make protein for 10-14 days, resulting in a “great” immune response, according to Dr. Weissman.
Most vaccines have an adjuvant, or something that stimulates the immune response by inducing TH1 or TH2 responses.
The LNP used in the COVID-19 vaccines is an adjuvant that makes a specialized CD4 helper cell that drives antibody production, increases antibody affinity, and matures antibodies to make long-lived plasma cells to allow for long-lived antibody responses.
This is the only adjuvant known that induces these type of helper T cells.

COVID-19 vaccine reactions

Adverse reactions to COVID-19 vaccination – flu-like symptoms, arm pain, etc. – are caused by the LNP, not the spike protein.
Once the LNP is gone, usually within the first 24 hours, symptoms dissipate.
The amount of spike protein produced decreases over 14 days.
It’s unclear if patients should take NSAIDs to manage symptoms after COVID-19 vaccination, as this hasn’t been tested.
However, with influenza vaccination, taking an NSAID will decrease the immune response.

Variants and their impact on vaccination

SARS-CoV-2 variants have been reported in Brazil, South Africa, California, and the United Kingdom.
Dr. Weissman explained that there are two kinds of variation: when a virus learns how to better infect people and when the virus learns to avoid immune responses.
Most SARS-CoV-2 variants are equally addressed by the vaccines, though we know vaccines have reduced efficacy against the South African variant, Dr. Weissman said.
The good news is that coronavirus mutates very slowly, and it’s easy with mRNA vaccines to “plug in” a mutant and make a more effective vaccine, Dr. Weissman said.

Vaccinating cancer patients: Treatment considerationsFor patients receiving chemotherapy:

We don’t know the best time to administer COVID-19 vaccines to patients on chemotherapy, as this hasn’t been studied, Dr. Weissman said.
When other vaccines were given to subjects receiving chemotherapy, those vaccines did not work as well.
Chemotherapy knocks down myeloid cells around day 7, with recovery typically around day 28.
Dr. Weissman said he would probably vaccinate at day 14 in the chemotherapy cycle, as the germinal centers where B cells are produced form about 2-7 days after receipt of the vaccine.

For patients receiving checkpoint inhibitors:

The optimal time for vaccination in patients receiving checkpoint inhibitors is unknown.
However, the immune response to vaccination in patients on checkpoint inhibitors is expected to be similar to the general population or slightly enhanced.

For patients receiving anti-CD20 antibodies:

Anti-CD20 antibodies might blunt the B-cell response to vaccination.
Rituximab, for example, depletes B cells in the circulation for months.
In the absence of B cells, there won’t be a good antibody response.
T-cell response is also stimulated by COVID-19 vaccines, but we don’t know how effective that response will be in protecting against infection, Dr. Weissman said.

Vaccinating HIV patients

Patients with well-controlled HIV (i.e., low viral load and CD4 counts >200) should generate a good immune response, Dr. Weissman said.
Patients with poorly controlled HIV (i.e., high viral loads and low CD4 counts) are likely to have a poor immune response to vaccination, though it isn’t clear how poor the response will be.

Should patients who recently had COVID-19 get vaccinated?

Clinicians are waiting 90 days to vaccinate patients who have a positive COVID-19 test, Dr. Weissman said.
In 95% of cases, SARS-CoV-2 infection conveys protective antibodies for at least 3 months.
Patients with recent SARS-CoV-2 infection have more severe adverse reactions to vaccination (e.g., fever, arm pain, flu-like symptoms).
It’s safe to wait until 2 weeks after recovery from infection before receiving the vaccine, and vaccination is expected to work well with a boosted immune response, Dr. Weissman said.

Is there any role for checking antibody status after vaccination?

Phase 3 trials of the Pfizer/BioNTech and Moderna vaccines showed that levels of neutralizing antibodies were higher in vaccinated patients than in those who had recently been infected; i.e., vaccines give a better immune response than infection.
The durability of response to the vaccines is unknown, but studies are underway.
The challenge for clinicians is that the antibody assays available are not directed at the spike protein, and they are not quantitative.

Vaccine on the horizon

The COVID-19 vaccine under development by Johnson & Johnson uses adenovirus.
The spike protein is inserted into the genome of the adenovirus, and the virus is altered so it cannot replicate, thus preventing its spread.
The live virus stimulates the cells to make a better immune response.
This type of vaccine is potent and produces lower antigen levels than mRNA vaccines but with better T-cell responses, Dr. Weissman said.
On Jan. 29, Johnson & Johnson released phase 3 data for this vaccine (https://bit.ly/3oNXX1k).
The vaccine was reported to be 85% effective overall in preventing severe COVID-19.

Show notes written by Sheila DeYoung, DO, a resident at Pennsylvania Hospital, Philadelphia.

Disclosures

Dr. Weissman disclosed royalties from Moderna and Pfizer/BioNTech. Dr. Henry has no disclosures.

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The greatest barrier to clinical trial enrollment is patients not knowing an appropriate trial exists, according to a survey of gynecologic cancer survivors.

The most common reason survey respondents gave for not enrolling in clinical trials was that their medical team didn't tell them about any trials.

Annie Ellis and Mary (Dicey) Jackson Scroggins – who are both patient advocates and ovarian cancer survivors – conducted this survey and presented the results at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer last year (https://bit.ly/3plI1Vg).

Ms. Ellis discussed the survey results and other related research with host David H. Henry, MD, in this episode.

Ms. Ellis and Ms. Scroggins distributed their 26-question survey online. The survey was completed by 189 survivors of gynecologic cancers.

Most respondents (65.6%) had never participated in a clinical trial. Reasons for nonparticipation included:

The medical team never discussed trial participation (50.4%)
The patient didn’t qualify for a trial (14.4%)
The trial location was too far away (7.2%)
The desired trial wasn’t available (4.0%)
Insurance didn’t cover trial participation (1.6%)
The patient didn’t want to receive a placebo (11.2%), wasn’t interested in experimental therapies (3.2%), didn’t want to be randomized (2.4%), or didn’t trust the medical system (1.6%)
Other reason (fill in the blank; 38.4%).

Roughly a third of respondents (34.4%) had participated in a clinical trial.

Most of these respondents (86.2%) learned about the trial from their doctor.
All past trial participants said they would participate again (84.6%) or they were not sure about future participation (15.4%).

Ms. Ellis also mentioned a recent review and meta-analysis, which showed that more than half of all cancer patients offered a clinical trial do participate (J Natl Cancer Inst. 2020 Oct 6. doi: 10.1093/jnci/djaa155. https://bit.ly/2Yg4dnP).

Together, these finding suggests cancer patients may be willing to participate in trials but often don’t know that relevant trials exist.

Ms. Ellis noted that her colleague, Ms. Scroggins, often says, “Patients can't go to the party if they don't get an invitation.”

Disclosures

Ms. Ellis, Ms. Scroggins, and Dr. Henry have no conflicts of interest.

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New studies have shed additional light on how convalescent plasma may affect patients with COVID-19, how blood type impacts bleeding risk, the effects of race on cancer-associated thrombosis, and iron deficiency in pregnancy.

These studies were presented as part of the “Best of ASH” session at the 2020 annual meeting of the American Society of Hematology.

Alisa S. Wolberg, PhD, of the University of North Carolina at Chapel Hill, who cochaired the session, reviews these studies with host David H. Henry, MD, in this episode.

Abstract #572: Association of ABO Blood Group with Bleeding Severity in Patients with Bleeding of Unknown Cause. https://bit.ly/2Mc0R2A.

This study, which included 422 patients, indicated that blood group O is overrepresented in patients with bleeding of unknown cause.
Blood group O was associated with a more severe bleeding phenotype, especially oral mucosal bleeding, independent of the levels of von Willebrand factor and factor VIII.
Patients with blood group O had increased clot density, but blood group O didn’t influence thrombin generation or platelet function analysis.
The researchers said these findings are important for better understanding the underlying mechanisms of bleeding in patients who have bleeding of unknown cause.
Dr. Wolberg said this study reframed how people look at bleeding of unknown cause.

Abstract #203: Racial/Ethnic Disparities in Cancer-Associated Thrombosis: A Population-Based Study. https://bit.ly/35Xi5HE.

This study included more than 942,109 cancer patients.
Results showed an independent association between race/ethnicity and the risk of cancer-associated thrombosis.
Asians/Pacific Islanders had a significantly lower incidence of cancer-associated thrombosis, compared with non-Hispanic Whites.
African Americans had a significantly higher incidence of cancer-associated thrombosis versus non-Hispanic Whites.
Racial/ethnic differences were especially prominent when examining pulmonary embolism only.
It’s hard to determine what causes these differences, Dr. Wolberg said. The differences could be explained by underlying biological traits, systemic racism, access to care, and/or the severity of underlying comorbidities, according to the researchers.

Abstract #424: Suboptimal Iron Deficiency Screening in Pregnancy in a High Resource Setting. https://bit.ly/2XYedSA.

The study included data on 47,590 pregnancies in 44,552 women from Ontario.
About 40% of these patients (n = 25,880) had ferritin measurements taken during pregnancy.
Iron deficiency was observed in 52.8% of evaluable pregnancies, and severe iron deficiency was seen in 23.8%.
These findings suggest a ferritin test should be included as part of routine bloodwork at the first prenatal visit, the researchers said.
They also noted that failing to evaluate iron stores in the second and/or third trimester misses the periods of highest iron-deficiency risk, when intravenous iron may be considered.
The researchers said these gaps in care should be addressed by revising guidelines.

Abstract #245: Efficacy of COVID-19 Pathogen-Inactivated Convalescent Plasma for Patients with Moderate-to-Severe Acute COVID-19: A Case-Matched Control Study. https://bit.ly/2XVlulU.

For this study, researchers compared 15 cases and 30 controls, all of whom had COVID-19.
Cases received two units of COVID-19 convalescent plasma (CCP) from different donors.
CCP appeared to improve survival in hospitalized COVID patients, though the difference was not significant.
The 28-day mortality rate was 6.7% among cases and 20.7% in controls (P = .233).
The researchers also found that unselected CCPs have heterogeneous antivirus activity.
Pathogen reduction treatment did not impact antivirus activity.
ADAP, ACE2, RVPN, and COVAM could be used to define activity.
A posttransfusion increase in activity could be detected in some, but not all, patients.
The researchers said more definitive studies are needed.

*Some of the data presented at the meeting differ from data included in the abstracts.

Disclosures:

Dr. Wolberg disclosed relationships with Bristol-Myers Squibb, GlaxoSmithKline, and Takeda. Dr. Henry has no financial disclosures relevant to this episode.

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Three studies revealed new findings on thrombosis in patients with cancer and/or COVID-19. These studies were presented at the 2020 annual meeting of the American Society of Hematology.

One study suggested the Khorana score may be ineffective for predicting venous thromboembolism (VTE) in cancer patients. Another study revealed factors that can predict VTE in patients with cancer and COVID-19. And a third study indicated that antithrombotic agents don’t improve outcomes in patients with severe COVID-19.

Kristen M. Sanfilippo, MD, of Washington University, St. Louis, reviews these studies with host David H. Henry, MD, in this episode.

Abstract 202: Performance of Khorana Score to Predict One-Year Risk of Venous Thromboembolism in Over Two Million Patients With Cancer. https://bit.ly/3oCHOfQ.

The study included 2,112,260 patients with cancer.
At 1 year after diagnosis, 227,170 (10.8%) patients had developed VTE.
The Khorana score was a weak to modest predictor of the 1-year risk of VTE (area under the curve, 0.565; 95% confidence interval, 0.564-0.566).

Abstract 204: Incidence of and Risk Factors for Venous Thromboembolism Among Hospitalized Patients With Cancer and COVID-19: Report From the COVID-19 and Cancer Consortium (CCC19) Registry. https://bit.ly/38waPnX.

The study included 1,813 hospitalized patients with COVID-19 and cancer who were enrolled in the CCC19 registry.
Patients had an increased risk of VTE if they had received anticancer therapy in the last 3 months (odds ratio, 1.63), had active disease (OR, 1.25 for stable/responding disease and 1.67 for progressing disease), had a cancer subtype with a high VTE risk (OR, 1.57 for high risk and 3.42 for very high risk), or were admitted to the ICU within 48 hours of hospitalization (OR, 2.38).
Patients had a reduced risk of VTE if they received preadmission anticoagulant (OR, 0.80) or antiplatelet therapy (OR, 0.71).
The researchers said this information will aid the development of a risk prediction tool for VTE in hospitalized patients with cancer and COVID-19.
For more information on the CCC19 registry, listen to the Blood & Cancer episode, “Studying cancer patients with COVID-19: NCCAPS and CCC19.” https://bit.ly/39lB0x0.

Abstract 206: Anticoagulant and Antiplatelet Use not Associated With Improvement in Severe Outcomes in COVID-19 Patients. https://bit.ly/3bvHqvV.

This retrospective study included 28,076 patients with confirmed COVID-19 – 1,024 of whom were on antiplatelet agents, anticoagulants, or both.
Chronic anticoagulant or antiplatelet use was not associated with a significantly lower risk of VTE (OR, 1.44), emergency department visit (OR, 0.94), ICU stay (OR, 0.87), or death (OR, 0.91).
However, anticoagulant or antiplatelet use was associated with a decreased risk of ventilator use (OR, 0.72).
Overall, these findings suggest chronic anticoagulant or antiplatelet use don't mitigate disease severity in COVID-19 patients, the researchers concluded.

The session in which these abstracts were presented is entitled, “904. Outcomes Research – Non-Malignant Conditions: Venous Thromboembolism Associated With Cancer and/or COVID-19,” and details can be found here: https://bit.ly/39olwIl.

Data in some of the abstracts differ from data presented at the meeting.

Disclosures

Dr. Sanfilippo disclosed relationships with Covington & Burling, Luther & Associates, Bayer, Health Services Advisory Group, and Amgen. Dr. Henry has no relevant disclosures.

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A number of groundbreaking and practice-changing studies were presented at the San Antonio Breast Cancer Symposium 2020.

The RxPONDER, ADAPT, and PRIME-2 trials revealed patients who can forgo chemotherapy or radiotherapy, monarchE and PENELOPE-B showed conflicting results with CDK4/6 inhibitors, one study indicated that a new tool can guide adjuvant chemotherapy, and another study suggested that circulating tumor cells (CTCs) can predict overall survival (OS).

Alan P. Lyss, MD, subprincipal investigator for Heartland Cancer Research NCORP, joined host David H. Henry, MD, to discuss these and other studies — their top 10 presentations from SABCS 2020 — in this episode.

1. Abstract GS3-07. Identifying patients whose symptoms are under-recognized during breast radiotherapy: Comparison of patient and physician reports of toxicity in a multicenter cohort. https://bit.ly/2MGCVEH

This presentation could be one of the most important stories to emerge from SABCS 2020, according to Dr. Lyss.
The trial included 9,868 breast cancer patients who received radiotherapy over an 8-year period.
Investigators compared patient and physician reports of toxicity during radiotherapy, assessing four symptoms: pain, pruritus, edema, and fatigue.
Physicians under-recognized moderate to severe pain 30.9% of the time, pruritus 36.7% of the time, edema 51.4% of the time, and fatigue 18.8% of the time.
“The bottom line is: We’ve got to do better at this, and the first step in correcting it is to acknowledge that there is a problem. This abstract established that,” Dr. Lyss said.

2. Abstract GS2-03. Prime 2 randomised trial (postoperative radiotherapy in minimum-risk elderly): Wide local excision and adjuvant hormonal therapy +/- whole breast irradiation in women =/> 65 years with early invasive breast cancer: 10-year results. https://bit.ly/3omINAL

The trial enrolled 1,326 women with histologically confirmed, unilateral invasive, hormone receptor-positive (HR+) breast cancer who were all 65 or older, had a tumor measuring 3 cm or less, had no nodal involvement, and were about to undergo breast-conserving surgery.
The women were randomized 1:1 to receive adjuvant whole-breast irradiation or no radiotherapy in addition to adjuvant endocrine therapy.
At 10 years, the rate of ipsilateral recurrence was significantly lower with radiotherapy than without it (0.9% vs 9.8%, P = .00008). The 10-year rate of regional recurrence was significantly lower with radiotherapy as well (0.5% vs. 2.3%, P = .014).
There was no significant difference in the radiotherapy and no-radiotherapy arms when it came to distant recurrence (3.6% vs. 1.9%, P = .07), contralateral recurrence (2.2% vs. 1.2%, P = .20), non–breast cancer (8.7% vs. 10.2%, P = .41), metastasis-free survival (96.4% vs. 98.1%, P = .28), or OS (81.0% vs. 80.4%, P = .68).
These results suggest radiotherapy could be omitted in this patient population, but the decision should be discussed and tailored to the individual patient, according to Dr. Henry.

3. Abstract GS1-01. Primary outcome analysis of invasive disease-free survival for monarchE: abemaciclib combined with adjuvant endocrine therapy for high-risk early breast cancer. https://bit.ly/38oSHwt

The monarchE trial enrolled 5,637 women with HR+, HER2- early breast cancer.
- Cohort 1 included patients with four or more positive nodes, up to three positive nodes and a tumor size ≥ 5 cm, or grade 3 disease.
- Cohort 2 included women with up to three positive nodes and a Ki-67 index ≥ 20%.
Patients in both cohorts were randomized to standard endocrine therapy alone or standard endocrine therapy with abemaciclib.
The 2-year rate of invasive disease-free survival (IDFS) was 92.3% in the abemaciclib arm and 89.3% in the control arm (P = .0009). The 2-year distant relapse-free survival rate was 93.8% and 90.8%, respectively (P = .0009).
Dr. Lyss said this is the first real advance in HR+ breast cancer adjuvant treatment in many years and has the potential to save thousands of lives. However, these are early data and should be interpreted with caution.

4. Abstract GS1-02. Phase III study of palbociclib combined with endocrine therapy (ET) in patients with hormone-receptor-positive (HR+), HER2-negative primary breast cancer and with high relapse risk after neoadjuvant chemotherapy (NACT): First results from PENELOPE-B. https://bit.ly/2XeQvRs

The PENELOPE-B trial enrolled 1,250 women who had completed neoadjuvant chemotherapy and locoregional therapy.
They were randomized to palbociclib plus endocrine therapy or endocrine therapy plus placebo.
There was no significant difference in IDFS with palbociclib or placebo at 2 years (88.3% vs. 84%), 3 years (81.2% vs. 77.7%), or 4 years (73% vs. 72.4%).

5. Abstract GS4-10. Development and validation of a tool integrating the 21-gene recurrence score and clinicopathologic features to individualize prognosis for distant recurrence and prediction of absolute chemotherapy benefit in early breast cancer. https://bit.ly/38htoMD

The RSClin tool integrates the 21-gene recurrence score and clinicopathologic features, including the grade of the tumor, the tumor size, and the patient's age.
Researchers found that RSClin could guide adjuvant chemotherapy in HR+, HER2-, axillary node-negative breast cancer with greater precision, when compared with clinicopathologic features or genomic data alone.
RSClin is available at https://online.genomichealth.com/.

6. Abstract GS4-08. Clinical utility of repeated circulating tumor cell (CTC) enumeration as early treatment monitoring tool in metastatic breast cancer (MBC) - a global pooled analysis with individual patient data. https://bit.ly/2MGUrZp

This study included 4,079 metastatic breast cancer patients who had undergone baseline and follow-up CTC measurements in previous trials.
The investigators analyzed changes in CTC levels between baseline and follow-up to determine whether those levels were associated with OS.
The median OS was 47 months for patients who were CTC-negative at both baseline and follow-up, 32.2 months for patients who were positive at baseline and negative at follow-up, 29.6 months for patients who were negative at baseline and positive at follow-up, and 17.8 months for patients who were positive at both time points.
With the negative-negative group as the reference, hazard ratios were 1.52 for the positive-negative group, 1.74 for the negative-positive group, and 3.15 for the positive-positive group (P < .0001 for all).

7. Abstract GS3-00. First results from a phase III randomized clinical trial of standard adjuvant endocrine therapy (ET) +/- chemotherapy (CT) in patients (pts) with 1-3 positive nodes, hormone receptor-positive (HR+) and HER2-negative (HER2-) breast cancer (BC) with recurrence score (RS) < 25: SWOG S1007 (RxPonder). https://bit.ly/35bK7Px

RxPONDER included 5,083 adults with HR+, HER2- breast cancer, one to three positive nodes, no contraindications to taxane and/or anthracycline-based chemotherapy, and recurrence scores of 25 or below.
Patients were randomized 1:1 to receive endocrine therapy or chemo-endocrine therapy using three stratification factors: recurrence score (0-13 vs.14-25), menopausal status, and axillary nodal dissection vs. sentinel node biopsy.
At a median follow-up of 5.1 years, there was no association between chemotherapy benefit and recurrence score values in the whole study population.
In postmenopausal patients, there was no difference in 5-year IDFS between patients who received chemotherapy and those who didn’t (91.6% vs. 91.9%, P = .82).
However, in premenopausal patients, the 5-year IDFS rate was 94.2% with chemotherapy and 89% without it (P = .0004).
The data also showed an OS benefit with chemotherapy in premenopausal patients (P = .032), although this result is considered early due to few deaths at the time of evaluation.
“These data really establish that postmenopausal women with between one to three involved nodes and an Oncotype DX score of 25 or less do not need post-operative adjuvant chemotherapy; end of discussion,” Dr. Lyss said. “For physicians who have been giving those women chemotherapy, these data are immediately practice- changing.”

8. Abstract GS4-04. Endocrine therapy alone in patients with intermediate or high-risk luminal early breast cancer (0-3 lymph nodes), Recurrence Score <26 and Ki67 response after preoperative endocrine therapy: Primary outcome results from the WSG-ADAPT HR+/HER2- trial. https://bit.ly/35edjVY

In this phase 3 trial, researchers combined static biomarkers (recurrence score in baseline core biopsy) and dynamic biomarkers (Ki-67 response) in an attempt to optimize adjuvant therapy in luminal early breast cancer.
The trial included 4,691 patients with HR+, HER2-negative, clinically high-risk disease who received about a month of standard endocrine therapy as neoadjuvant treatment.
Patients with a pretreatment recurrence score of 0-11 continued endocrine therapy alone with no planned chemotherapy at all.
Patients with a pretreatment recurrence score of 12-25 received their month of endocrine therapy and then had a core biopsy of their residual tumor. If the Ki-67 had dropped to less than 10%, the patient continued endocrine therapy alone. If the Ki-67 remained > 10% or the patient had clinical N2 or N3 lymph nodes, the patient was assigned to receive neoadjuvant chemotherapy.
The 5-year IDFS rate was 92.6% in patients with a recurrence score of 12-25 and a Ki-67 response and 93.9% in patients with a recurrence score of 0-11.
The 5-year distant relapse-free survival was 95.6% and 96.3%, respectively. The 5-year OS was 97.3% and 98%, respectively.
These results suggest Oncotype DX testing could spare the majority of HR+, HER2- patients with zero to three positive lymph nodes from receiving chemotherapy, Dr. Lyss said.

9. Abstract GS3-01. Additional efficacy endpoints from the phase 3 KEYNOTE-355 study of pembrolizumab plus chemotherapy vs placebo plus chemotherapy as first-line therapy for locally recurrent inoperable or metastatic triple-negative breast cancer. https://bit.ly/394UCVX

In KEYNOTE-355, 847 patients with locally recurrent, inoperable or metastatic triple-negative breast cancer were randomized to receive pembrolizumab plus chemotherapy or chemotherapy plus placebo. Chemotherapy consisted of nab-paclitaxel, paclitaxel, or gemcitabine plus carboplatin.
The median progression-free survival (PFS) was longer in the pembrolizumab arm, at 7.5 months, versus 5.6 months with chemotherapy alone (hazard ratio, 0.82).
The PFS was superior with pembrolizumab regardless of the chemotherapy partner.
However, higher PD-L1 expression was associated with a longer PFS, a higher overall response rate, and a longer duration of response.

10. Abstract GS3-06. Biomarker evaluation in the phase 3 ASCENT study of sacituzumab govitecan versus chemotherapy in patients with metastatic triple-negative breast cancer. https://bit.ly/3hQ14nJ

Trophoblast cell-surface antigen-2 (Trop-2) is highly expressed in triple-negative breast cancer.
Sacituzumab govitecan (SG) consists of an anti-Trop-2 antibody coupled to SN-38, an active metabolite of irinotecan.
In the ASCENT trial, patients with metastatic triple-negative breast cancer were randomized to SG or standard single-agent chemotherapy.
A subgroup analysis of this trial showed that Trop-2 levels correlated with PFS and OS.
Patients were divided into three groups by Trop-2 levels — low (H-score <100), medium (100-200), and high (200-300).
In patients with low Trop-2 levels, the median PFS was 2.7 months with SG and 1.6 months without it. The median OS was 9.3 months and 7.6 months, respectively.
In patients with medium Trop-2 levels, the median PFS was 5.6 months with SG and 2.2 months without it. The median OS was 14.9 months and 6.9 months, respectively.
In patients with high Trop-2 levels, the median PFS was 6.9 months with SG and 2.5 months without it. The median OS was 14.2 months and 6.9 months, respectively.

*Some of the numbers mentioned in this episode are incorrect, but the correct numbers are reflected in the show notes. The data presented at SABCS 2020 sometimes differed from data included in the abstracts.

Disclosures:

Dr. Henry has no financial disclosures relevant to this episode.

Dr. Lyss writes a column for MDedge Hematology/Oncology called “Clinical Insights.” He has no other conflicts of interest.

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In this episode, we bring you clips from the best Blood & Cancer shows of 2020. Blood & Cancer will be back with new episodes in 2021.

ESMO 2020: Late-breaking and practice-changing studies on COVID-19 and breast, lung, gastrointestinal, and other cancers
https://bit.ly/3h7aWZM
Beyond the lungs: How COVID-19 affects the blood, brain, gastrointestinal system, and other organ systems
https://bit.ly/37GhV8Q
EHA25: AML, myeloma, polycythemia vera, and COVID-19 with EHA President John Gribben
https://bit.ly/3nS4592
VTE rate, 'COVID toes,' and Virchow's triad: What you need to know about COVID and coagulation
https://bit.ly/3rizmnM
ASCO 2020: Practice-changing studies in breast, lung, colorectal, and other cancers
https://bit.ly/37EIbkg

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News from SABCS 2020:

RxPONDER: Even more women may forgo chemo for breast cancer: https://bit.ly/2LIYjZt
Breast surgery may be a gateway to addictive medication use: https://bit.ly/3gSWfJF
Pregnancy after breast cancer is rockier but doesn’t increase recurrence risk: https://bit.ly/2KwlhCx

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The ASH Research Collaborative COVID-19 Registry for Hematology was established earlier this year to study patients with hematologic malignancies diagnosed with COVID-19. Now, the registry also includes patients with nonmalignant hematologic disorders and hematologic manifestations of COVID-19.

William Wood, MD, of the University of North Carolina at Chapel Hill, recently presented data from the registry at the ASH Annual Meeting. In this episode, Dr. Wood tells host David H. Henry, MD, how the registry came to be and reviews some of its findings.

About the registry

The registry is part of the ASH Research Collaborative, an organization established in 2018 to foster collaboration to accelerate progress in hematology.
The registry houses data on patients with a COVID-19 diagnosis and hematologic disorders/malignancies or hematologic manifestations of COVID-19.
Health care providers around the world can contribute data to the registry.
Anyone can view summaries of the deidentified data on the registry website.
The website data are updated every day or every few days.
The information compiled in the registry includes:
- The nature of patients’ underlying disease
- Treatments received until COVID-19 diagnosis
- Sociodemographic information
- COVID-19 symptoms and time to resolution or death
- COVID-19–directed treatments
- Expected prognosis
- Whether patients opted for intensive care.

Registry findings

The registry data presented at ASH 2020 included 656 patients with hematologic malignancies and COVID-19.
Dr. Wood said the first conclusion drawn from these data is that patients with underlying hematologic malignancies are a “medically vulnerable population” when it comes to COVID-19.
The mortality rate was 20% overall and 33% in patients with hospitalization-level severity.
The other major finding, Dr. Wood said, is that the risk of severe COVID-19 and death is differentially distributed.
Risk factors for adverse COVID-19 outcomes include:
- Increasing age
- Advanced underlying disease or limited prognosis
- Forgoing intensive management.

Relevant links

ASH Research Collaborative: https://bit.ly/37pczyV.
COVID-19 Registry for Hematology: https://bit.ly/3r1U9vO.
Blood Adv. 2020. 4(23):5966-75. https://bit.ly/34jWVTt.
Wood W et al. ASH 2020, Abstract 215. https://bit.ly/3gRzw0A.

Disclosures

Dr. Wood disclosed research funding from Pfizer, consultancy for Teladoc/Best Doctors, and honoraria from the ASH Research Collaborative. Dr. Henry has no relevant disclosures.

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News from ASH 2020:

No benefit from tranexamic acid prophylaxis in blood cancers: https://bit.ly/2K3Mah1
‘Practice changing’: Ruxolitinib as second-line in chronic GVHD: https://bit.ly/3gT4kyg
Durable responses with anti-BCMA CAR T-cell for multiple myeloma: https://bit.ly/381f1ut
Five-minute SC injection of daratumumab in RRMM: https://bit.ly/3gKuZgx

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A pair of biomarkers are being used to guide treatment and predict mortality in patients with graft-versus-host disease (GVHD), according to James L.M. Ferrara, MD, DSc, of the Icahn School of Medicine at Mount Sinai, New York.

In this episode, Dr. Ferrara explains how measuring these biomarkers – REG3-alpha and ST2 – can prevent over- and undertreatment of acute GVHD. The biomarkers have also been shown to predict nonrelapse mortality more accurately than a change in clinical symptoms.

Before reviewing these findings, Dr. Ferrara tells host David H. Henry, MD, what GVHD is, how to recognize it, and how it’s typically treated.

GVL and GVHD

GVHD is “very tightly associated” with the graft-versus-leukemia (GVL) effect, Dr. Ferrara explained.
The GVL effect refers to the ability of donor immune cells to eliminate host malignant cells after allogeneic hematopoietic stem cell transplant (allo-HSCT).
The donor T cells respond to minor histocompatibility antigens on malignant cells but also on normal cells.
When the donor T cells attack the normal cells, the patient develops GVHD.
To prevent GVHD, patients may receive cyclosporin, tacrolimus, methotrexate, sirolimus, or other drugs in various combinations.
Despite prophylaxis, slightly under half of allo-HSCT recipients will still develop some form of GVHD, Dr. Ferrara said.

Acute GVHD

Acute GVHD typically occurs in the first month or two after transplant, and about 50% of cases happen in the first month, Dr. Ferrara said.
There are three primary targets – the skin, liver, and GI tract.
The rash observed with skin GVHD is vesiculopapular, and the extent of the rash determines the stage of GVHD in the skin.
Increase in total bilirubin is used to measure the stages of liver disease.
GVHD in the GI tract is characterized by persistent nausea and vomiting or diarrhea (up to liters a day).
Evaluating the skin, liver, and GI tract together can provide the overall GVHD grade, between 1 and 4.
Grade 4 GVHD is the most severe, and grade 1 is a skin rash that usually affects less than 50% of the body surface area.

Over- and undertreatment

When GVHD is mild and limited to the skin, topical steroid creams are adequate treatment.
When GVHD progresses into the GI tract and liver, patients require systemic immunosuppression.
However, it’s difficult to tell whether GVHD is going to be mild, moderate, or severe.
So when patients with acute GVHD receive systemic steroids at a starting dose of 1 mg/kg, many of these patients are overtreated “and a fair number of them are undertreated because we don't actually know which patients are going to progress and which patients are going to respond to treatment,” Dr. Ferrara said.
He noted that the JAK1/2 inhibitor ruxolitinib was approved to treat steroid-refractory acute GVHD last year. Prior to that, the only approved treatment for GVHD was systemic steroids.

Biomarkers signal disease severity

Through their research, Dr. Ferrara and colleagues identified two biomarkers of GVHD severity – REG3-alpha and ST2.
“When the GI tract is damaged early, these proteins flood into the systemic circulation, and they can actually tell us who's got a damaged GI tract very early, even before one has symptoms like diarrhea,” Dr. Ferrara explained.
The biomarkers can be used to assess, at the onset of GVHD, whether or not a patient has crypt damage and needs more intensive treatment.

Biomarkers guide treatment, predict outcomes

Dr. Ferrara and colleagues used serum samples collected by the Mount Sinai Acute GVHD International Consortium (MAGIC) to develop MAGIC Algorithm Probability (MAP).
MAP is calculated from patients’ levels of REG3-alpha and ST2 and can be used to predict the risk of severe GVHD.
“You put these two biomarkers into an equation, you get a single number, and that number tells you whether [the patient is] high risk, low risk, or intermediate risk,” Dr. Ferrara explained.
He and his colleagues found they could use MAP to predict patients’ response to treatment and mortality.
In fact, MAP was able to predict nonrelapse mortality more accurately than a change in clinical symptoms (Blood Adv. 2019. 3[23]:4034-42. https://bit.ly/39QNUVn).

Standard practice, ongoing trials

MAP is increasingly becoming a part of standard practice, Dr. Ferrara said.
A company called Viracor Eurofins Clinical Diagnostics licensed MAP and provides tests for consumer use (https://bit.ly/33RhRBa).
Centers can send blood samples to Viracor to test.
More than 50 centers in the United States sent at least 1,000 samples to Viracor for testing in 2019, Dr. Ferrara said.
He and his colleagues are also utilizing MAP in ongoing clinical trials:
- A phase 2 study of natalizumab plus standard steroid treatment for high-risk acute GVHD (NCT02133924; https://bit.ly/3grvsUK).
- A pilot trial of alpha1-antitrypsin for preemption of steroid-refractory acute GVHD (NCT03459040; https://bit.ly/3qy48c9).
- A phase 2 trial of itacitinib for low-risk GVHD (NCT03846479; https://bit.ly/37GkaYK).

Disclosures:

Dr. Ferrara has a patent for serum biomarkers of acute GVHD and receives royalties from Viracor. Dr. Henry has no relevant disclosures.

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Blood & Cancer news stories:

Black patients with ES-SCLC get less chemo but have better survival: https://bit.ly/33Rb5eB
Should CTCs guide treatment choice in HR+, HER2– breast cancer?: https://bit.ly/3gn6shc
New drug approved for relapsed/refractory neuroblastoma: https://bit.ly/2VMpvIy
FDA approves first agent for PSMA-PET imaging in prostate cancer: https://bit.ly/36TAaY7

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Researchers are conducting the first U.S. trial of pressurized intraperitoneal aerosolized chemotherapy (PIPAC) for the treatment of peritoneal carcinomatosis in patients with gynecologic or gastrointestinal cancers.

Coprincipal investigator Thanh H. Dellinger, MD, of City of Hope in Duarte, Calif., describes this trial and the PIPAC procedure to host David H. Henry, MD, in this episode.

To start, the pair discuss a patient who might be eligible for PIPAC – one with stage 3 ovarian cancer.

General approach to stage 3 ovarian cancer

Therapy typically includes a combination of surgery and chemotherapy.
The order in which chemotherapy is given, either pre- or postoperatively, depends on performance status and whether patients have extra-abdominal disease or parenchymal liver disease.
Operative approaches, including debulking surgery, are pursued if believed to be optimal, meaning all gross residual disease can be resected.
If all residual disease cannot be resected, patients are offered neoadjuvant chemotherapy, typically for three to four cycles before an interval debulking surgery, followed by postoperative adjuvant chemotherapy.

Intraperitoneal chemotherapy

Intraperitoneal (IP) chemotherapy is used to treat peritoneal surface malignancies.
The peritoneum is a separate organ that is difficult to treat adequately with intravenous chemotherapy alone.
Giving IP chemotherapy in combination with intravenous chemotherapy may be more effective than intravenous chemotherapy alone (N Engl J Med. 2006; 354:34-43; https://bit.ly/3g3lngx).
However, there are many challenges in delivering IP chemotherapy, including increased side effects of abdominal pain and IP catheter failure.
Recent clinical trials have shown that, with the addition of bevacizumab, the survival benefit with IP chemotherapy may not be as significant as prior trials suggested (J Clin Oncol. 2019 Jun 1;37[16]:1380-90; https://bit.ly/2VAmRVW).
In general, IP chemotherapy has not been embraced by the medical oncology community as much other types of chemotherapies, Dr. Dellinger said.

What is PIPAC?

PIPAC is a novel therapy discovered by a German surgical oncologist, Marc A. Reymond, MD, from University of Tuebingen (Germany).
PIPAC delivers chemotherapy at a reduced dose directly into the intraperitoneal cavity but in a pressurized and aerosolized form.
PIPAC is done at the time of the diagnostic laparoscopy and requires a nebulizer for aerosolization of the chemotherapy as well as a high-pressure injector.
This approach allows for the chemotherapy to be pushed deeper into tissues, compared with hyperthermic intraoperative peritoneal chemotherapy (HIPEC).
With HIPAC, tissue penetration is typically 1 mm or less. With PIPAC, there is deeper penetration and better distribution of chemotherapy throughout the entire intraperitoneal cavity.
With PIPAC, chemotherapeutic agents are given at a lower dose than is typically administered with IP or intravenous chemotherapy, which helps in reducing the toxicity.
PIPAC is given every 6 weeks for three cycles, requiring three laparoscopic procedures.
These laparoscopic procedures allow for the opportunity to obtain peritoneal tumor biopsies before and after to investigate the natural course of these tumors and their microenvironment.

Toxicity of PIPAC

PIPAC has been done in more than 800 patients with gastrointestinal and gynecologic cancers in Europe and Asia.
Severe adverse events have been minimal, with about 12%-15% grade 3/4 SAEs and very rare grade 5 SAEs.
The most common side effect is typically abdominal pain, attributed to the IP administration in conjunction with the laparoscopic surgery.
Renal toxicity is a concern with intravenous cisplatin use, but this has not yet been seen with PIPAC.
With PIPAC, cisplatin is given at 10.1 mg/m2 and doxorubicin is given at 2.1 mg/m2, doses that are much lower than the typical doses for these drugs.

PIPAC in clinical trials

PIPAC clinical trials have moved into phase 2 in Europe for ovarian cancer, with a publication demonstrating an objective response rate of over 60% in platinum-resistant ovarian cancer (Gynecol Oncol. 2015 May;137[2]:223-8; https://bit.ly/2KY701r).
A phase 3 trial of PIPAC was planned but was stalled because of the COVID-19 pandemic.
Because of the need for Food and Drug Administration approval, researchers have just launched the first phase 1 trial of PIPAC in the United States.

Phase 1 trial of PIPAC

City of Hope is working with affiliates at Mayo Clinic in Jacksonville, Fla.; Northwell Health in New York; and the National Institutes of Health to enroll eligible candidates for a phase 1 trial (NCT04329494; https://bit.ly/3qs8H7U).
Eligible candidates include those with gastric, uterine, colorectal, appendiceal, and ovarian cancer with evidence of peritoneal carcinomatosis who have failed at least one line of therapy.
PIPAC is an outpatient procedure, but given the trial and need for monitoring, patients typically leave the hospital the following day after blood samples are obtained for the study.
City of Hope has recruited seven patients since activating their study in August 2020, with a goal of enrolling 16 patients by spring 2021.

Future directions

Peritoneal tumor biopsies obtained during the laparoscopic procedures are being used to study the microenvironment of these cancers.
In eventual phase 2 clinical trials, the researchers may include immune checkpoint inhibitors.
Biomarker analyses are underway, looking at expression of PD-1 and tumor-infiltrating lymphocytes.
The researchers are also studying the role of genomic sequencing and DNA repair.

Disclosures:

Dr. Dellinger and Dr. Henry have no financial disclosures relevant to this episode.

Show notes by Sheila De Young, DO, resident at Pennsylvania Hospital, Philadelphia.

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Blood & Cancer News Stories:

Immune checkpoint inhibitors don’t increase COVID-19 incidence or mortality, studies suggest: https://bit.ly/2JlP2FN
HCC rates slow in cities, continue to climb in rural areas: https://bit.ly/2Jx6Ux1
Risk factors for severe immune-related AEs identified: https://bit.ly/3fO6Fd8

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In this episode, host David H. Henry, MD, highlights some recent articles from Blood, the Journal of Clinical Oncology, and the New England Journal of Medicine.

Blood

How I Treat series on hematologic complications in pregnancy. https://bit.ly/3fr5nV8
Mutational and phenotypic characterization of hereditary hemorrhagic telangiectasia. https://bit.ly/3nQvhF6

Journal of Clinical Oncology

Hepatitis B Virus Screening and Management for Patients With Cancer Prior to Therapy: ASCO Provisional Clinical Opinion Update. https://bit.ly/3maTOE4
- Related Blood & Cancer episode:
  Cancer and hepatitis B virus: ASCO's recommendations for HBV screening, monitoring for reactivation, and how to treat patients. https://bit.ly/3m0jjrF
- Chemotherapy and Venetoclax in Elderly Acute Myeloid Leukemia Trial (CAVEAT): A Phase Ib Dose-Escalation Study of Venetoclax Combined With Modified Intensive Chemotherapy. https://bit.ly/372FFCB
- Chemotherapy and COVID-19 Outcomes in Patients With Cancer. https://bit.ly/35WRLOi
- Related Blood & Cancer episodes:
  Studying cancer patients with COVID-19: NCCAPS and CCC19. https://bit.ly/3pYl2Au
  TERAVOLT registry sheds light on patients with thoracic cancers and COVID-19. https://bit.ly/2URdwJh
- Diffuse Large B-Cell Lymphoma’s New Genomics: The Bridge and the Chasm. https://bit.ly/36XdGnY

New England Journal of Medicine

Osimertinib in Resected EGFR-Mutated Non–Small Cell Lung Cancer. https://bit.ly/2J5q7FQ
Humoral Immune Response to SARS-CoV-2 in Iceland. https://bit.ly/2USw7ET
Low-Dose Edoxaban in Very Elderly Patients with Atrial Fibrillation. https://bit.ly/39aM0ia
Remdesivir for the Treatment of COVID-19 – Final Report. https://bit.ly/375dYJk
Remdesivir for 5 or 10 Days in Patients with Severe COVID-19. https://bit.ly/2IZJ7Wq

Disclosures:

Dr. Henry has no relevant disclosures.

For more MDedge Podcasts, go to mdedge.com/podcasts

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In this episode, we discuss updated guidelines on the screening and management of hepatitis B virus (HBV) in patients about to start anticancer therapy. The guidelines come from an American Society of Clinical Oncology Provisional Clinical Opinion (PCO) published earlier this year.

Jessica P. Hwang, MD, of MD Anderson Cancer Center, and Andrew Artz, MD, of City of Hope, are cochairs of the ASCO PCO. They joined host David H. Henry, MD, to discuss the guidelines.

Epidemiology of HBV

Data suggest chronic HBV infection affects 257 million people globally.
In the United States, chronic HBV infection has a prevalence of less than 1%, but the prevalence of past HBV can be 5%-40% in high-risk populations.
High-risk populations include people born in endemic areas (i.e., Africa, Asia, and South America), those with injection drug use, men who have sex with men, and people with household contacts who have HBV.
In patients with cancer, the prevalence of past HBV infection is 5%-10%, with a 0.5% prevalence of chronic HBV.

HBV and oncology: Who should be screened?

The ASCO PCO recommends universal HBV screening in all patients planning or undergoing anticancer therapy.
To screen, practitioners should order three tests before initiating anticancer therapy: hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc) total immunoglobulin (Ig) or IgG, and hepatitis B surface antibody (anti-Hbs).

Interpretation of serology

Chronic infection: HBsAg (+), anti-HBc (+), anti-HBs (-).
Resolved past infection: HbsAg (-), anti-HBc (+), anti-HBs (+).
Past infection, isolated core: HbsAg (-), anti-HBc (+), anti-HBs (-).
Vaccine-induced immunity: HbsAg (-), anti-HBc (-), anti-HBs (+).

Recommended treatment and/or monitoring

Once a patient is infected, the HBV incorporates into the host genome and can live latently, so the patient is at risk of reactivation with immunosuppressive anticancer therapy (with chronic or past infection).
Certain therapies pose a heightened risk of HBV reactivation, including anti-CD20 monoclonal antibodies and stem cell transplant.
Patients receiving checkpoint blockade immunotherapy should be monitored closely for reactivation, though autoimmune hepatitis and high-dose steroids used in treating immune-related events could confound the reactivation of HBV.
Further guidelines specific to checkpoint blockade immunotherapy are dichotomized and can be found in the ASCO PCO.
In patients with chronic HBV infection receiving any systemic anticancer therapy, the ASCO PCO recommends antiviral prophylactic therapy during anticancer therapy and for a minimum of 12 months after anticancer therapy, with consultation of an HBV specialist.
Entecavir, tenofovir disoproxil fumarate, and tenofovir alafenamide are well tolerated and have a low rate of viral resistance, making them favorable for patients who need to be treated.

Implementing a screening program

Recommend a multidisciplinary team approach, including physicians, pharmacists, and public health professionals.
Utilize EHRs to incorporate alerts for screening and embedding screening into order sets.
Ensure that positive test results are delivered to the appropriate medical team.
Link patients into care for treatment and/or monitoring.

Source and resources

The ASCO PCO was published in the Journal of Clinical Oncology: https://bit.ly/3pClNPo.
Additional resources are available on the ASCO website: https://bit.ly/35E0nt0.
An infographic is also available: https://bit.ly/3pBuE3K.

Show notes written by Sheila DeYoung, DO, a resident at Pennsylvania Hospital, Philadelphia.

Disclosures

Dr. Hwang disclosed relationships with Gilead Sciences, Merck Sharp & Dohme, and the Asian Health Foundation. Dr. Artz disclosed research funding from Miltenyi Biotec. Dr. Henry has no relevant disclosures.

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The Tomosynthesis Mammography Imaging Screening Trial (TMIST) was designed to see if 3-D mammography, or tomosynthesis, could help personalize screening and if 3-D is actually better than the less expensive 2-D mammography.

TMIST is the largest breast cancer screening trial in the United States, with a cost of $100 million and a planned enrollment of 165,000 women.

There's just one problem. The study is falling short on enrollment of patients and participating sites. Will this mean the death of TMIST?

For more details, see coverage of TMIST on Medscape:
NCI May 'Kill' Major Mammography Trial, Says Advisor
https://www.medscape.com/viewarticle/937918

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Can receiving all posttransplant care at home benefit patients undergoing hematopoietic stem cell transplant (HSCT)? Researchers are conducting phase 2 trials to find out.

Anthony D. Sung, MD, of Duke University School of Medicine, described this research to host David H. Henry, MD.

Dr. Sung outlined the process of receiving post-HSCT care at home and discussed Duke's clinical trials assessing the impact of home care on costs, quality of life, the microbiome, and graft-versus-host disease (GVHD).

Dr. Sung also discussed another Duke trial investigating whether a probiotic can prevent COVID-19.

Post-HSCT care at home: How it works

Cell collection (if applicable), conditioning, and HSCT all take place in the outpatient setting.
From day 1 after transplant onward, the patient receives all care at home.
A nurse practitioner or physician assistant visits the patient every morning to draw labs, which are run at the hospital.
A nurse visits every afternoon to give the patient supportive care.
Patients are given the tools to video chat with physicians.
Patients must live within 1 hour of Duke’s transplant center or relocate to furnished apartments near the transplant center.

Phase 1 trial: Feasible and safe

Dr. Sung and colleagues have completed a phase 1 trial, which suggested that post-HSCT care at home was feasible and safe.
Outcomes were similar to outcomes in patients who do not receive post-HSCT care at home.
The results were presented at ASH 2017 (Blood. 2017;130:745; https://bit.ly/2UelgVo).

Phase 2 trials: Microbiome, GVHD, and other outcomes

With one phase 2 trial (NCT01725022), Dr. Sung and colleagues aim to determine if:
- Patients can maintain their normal bowel microbiota by receiving post-HSCT care at home, as opposed to outpatient or inpatient care.
- Treatment-related morbidities and mortality are similar between the groups.
- Care at home improves quality of life and reduces costs.
Trial details can be found here: https://bit.ly/2JRnY0Y.
In the other phase 2 trial (NCT02218151), the main goal is to compare the incidence of grade 2-4 acute GVHD at 6 months in patients receiving care at home vs. inpatient or outpatient care.
- The theory is that maintaining the microbiome will reduce the risk of GVHD.
- A case of GVHD can add $100,000 to the cost of care, Dr. Sung noted.
Trial details can be found here: https://bit.ly/32vr8y3.

COVID-19 and the microbiome

Dr. Sung and colleagues are also conducting a trial of Lactobacillus rhamnosus GG (LGG) as prophylaxis for COVID-19 (NCT04399252).
Research has shown that giving LGG to mice with Pseudomonas aeruginosa pneumonia can:
- Help prevent lung injury and significantly improve survival (Shock. 2013;40[6]:496-503; https://bit.ly/3khQBRr).
- Help modulate the microbiome and immune system, leading to decreased inflammation, TNF-alpha, IL-2, and IL-6, as well as increased regulatory T cells (Clin Nutr. 2017;36[6]:1549-1557; https://bit.ly/35lENJZ).
Dr. Sung noted that TNF-alpha, IL-2, and IL-6 have also been implicated in COVID-19 and associated with increased lung injury.
Dr. Sung and colleagues have theorized that LGG could decrease lung injury and the symptoms of COVID-19 and perhaps even prevent COVID-19.
The researchers are conducting a randomized trial of LGG in household contacts of patients with COVID-19 (https://bit.ly/2GRSC9x).
For more details on the trial, email protect-ehc@duke.edu or visit https://bit.ly/2IsLjWh.

Disclosures:

Dr. Sung and Dr. Henry have no relevant disclosures. Duke's transplant trials are funded by grants from the National Institutes of Health. Funding for the COVID-19 trial is provided by the Duke Microbiome Center and philanthropic giving. The LGG and placebo used in the trial are provided by DSM.

For more MDedge podcasts, visit mdedge.com/podcasts

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Hematology Oncology News:

IMRT new standard of care for high-risk cervical cancer: https://bit.ly/3k7ji3y
Real-world results with checkpoint inhibitors found inferior to trial results: https://bit.ly/35cIt0v
Are HMAS appropriate for posttransplant maintenance in acute leukemias?: https://bit.ly/3lfqsE7

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In this episode, we review how immune checkpoint inhibitors and COVID-19 have changed the management of non-small cell lung cancer (NSCLC).

Jeffrey Crawford, MD, and Susan Blackwell, PA, both of Duke Cancer Institute, join host David H. Henry, MD, to discuss the use of pembrolizumab in NSCLC, two studies of PD-1 inhibitors presented at ESMO 2020, and how COVID-19 has affected NSCLC care, particularly the use of granulocyte colony-stimulating factor (G-CSF).

Diagnosis and treatment of NSCLCWhat information should be obtained from a biopsy?

Is this lung cancer?
If so, what kind of lung cancer is it: Small-cell lung cancer or NSCLC? Which subtype?
Molecular studies for targets, including ALK, KRAS, EGFR, PD-L1.

Treatment with pembrolizumab:

If, for example, a patient has NSCLC and is positive for PD-L1, the treatment of choice is pembrolizumab.
A multidisciplinary approach is essential to provide comprehensive education and care to patients taking pembrolizumab (and other immunotherapies).
Pembrolizumab can have many side effects, including itching, fatigue, thyroiditis progressing to hypothyroidism, hypophysitis, or another off-target “-itis.”
Ms. Blackwell and Dr. Crawford recommend listening to patients, checking the thyroid routinely, and checking cortisol based on index of suspicion.

NSCLC studies presented at ESMO 2020 KEYNOTE-024 5-year OS update: First-line (1L) pembrolizumab (pembro) vs platinum-based chemotherapy (chemo) in patients (pts) with metastatic NSCLC and PD-L1 tumour proportion score (TPS) ≥50%.

The 5-year survival is greater than 30% with pembrolizumab in this study.
Historically, 5-year survival has been 1% to 2% in patients treated with chemotherapy alone, Dr. Crawford said.
In the control arm of this study, patients received chemotherapy and then crossed over into the pembrolizumab arm, so overall survival was 16% at the 5-year mark.
The results suggest immunotherapy should be used first-line if patients meet criteria, Dr. Crawford said.
Source: Abstract LBA51. https://bit.ly/3mMYLTK.

EMPOWER-Lung 1: Phase III first-line (1L) cemiplimab monotherapy vs platinum-doublet chemotherapy (chemo) in advanced non-small cell lung cancer (NSCLC) with programmed cell death-ligand 1 (PD-L1) ≥50%.

Cemiplimab improved overall and progression-free survival in NSCLC patients when compared with chemotherapy alone.
Abstract LBA52. https://bit.ly/3mLT6xb.

The effects of COVID-19 on NSCLC care

Logistically, it’s more difficult to see patients during the pandemic, Dr. Crawford noted, but the many potential side effects of immunotherapy make it necessary to see patients regularly in person.

How has COVID-19 affected the concern of febrile neutropenia and the use of G-CSF? Dr. Crawford said the pandemic has heightened the concern about infection risk.

Prior guidelines for G-CSF:

Before the pandemic, guidelines suggested routine prophylactic G-CSF in patients with a greater than 20% risk of febrile neutropenia.
In patients with 10% to 20% risk, the recommendation was to consider the use of G-CSF based on the patient population and risk factors.

Pandemic-specific guidelines for G-CSF:

The National Comprehensive Cancer Network (NCCN) recommended relaxing guidelines during the pandemic.
If the risk is greater than 20%, NCCN still recommends giving G-CSF.
If the risk is 10% to 20%, NCCN recommends giving G-CSF even in the absence of additional risk factors.
Dr. Crawford noted that lung cancer patients receiving chemotherapy are typically in the 10% to 20% risk category.
Download the COVID-specific NCCN guidelines: https://bit.ly/3jQIco5.

G-CSF biosimilars

The most common complaint with biosimilars is bone pain.
Ms. Blackwell advises first treating bone pain with acetaminophen or ibuprofen and warm blankets.
For refractory pain, she suggests a low-dose narcotic or dexamethasone.
Consider an antihistamine for prophylaxis, as patients report this can help with symptoms.

Show notes written by Ronak Mistry, DO, a resident at Pennsylvania Hospital, Philadelphia.

Disclosures:Dr. Crawford is on advisory boards at Amgen and Merck, makers of Onpro/Neulasta (pegfilgrastim) and Keytruda (pembrolizumab). Ms. Blackwell and Dr. Henry have no conflicts of interest.

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News from MDedge Hematology-Oncology:

New estimates for breast cancer risk with HRT: https://bit.ly/37VT0Pt
BMJ study: https://bit.ly/2TKDIVt
Lancet meta-analysis: https://bit.ly/3kUdbRl
Single and multifraction SBRT found comparable for lung metastases: https://bit.ly/2HS36pR
Statins may lower risk of colorectal cancer: https://bit.ly/3kLbR37

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In this episode, we review the latest guidelines on antiemetics from the American Society of Clinical Oncology (ASCO).

Host David H. Henry, MD, is joined by ASCO guideline author Paul J. Hesketh, MD, of Lahey Hospital and Medical Center in Burlington, Mass.

Dr. Hesketh explains the recommendations for antiemetic use in cancer patients receiving checkpoint inhibitors (CPIs) or high-, moderate-, or low-emetic-risk antineoplastic agents.

Checkpoint inhibitorsThe update to ASCO’s guidelines was primarily driven by questions about antiemetic use in patients receiving CPIs, according to Dr. Hesketh.

After a literature review, Dr. Hesketh and coauthors concluded that:

Patients receiving CPIs alone do not require an antiemetic regimen.
When CPIs are given with chemotherapy, there is no need to modify the antiemetic regimen.
Dexamethasone does not compromise the efficacy of CPIs.

High-emetic-risk antineoplastic agents

Adults treated with cisplatin and other high-emetic-risk single agents should be offered a four-drug combination: an NK1 receptor antagonist, a serotonin (5-HT3) receptor antagonist, dexamethasone, and olanzapine on day 1. Dexamethasone and olanzapine should be continued on days 2-4, as cisplatin can cause delayed emesis.
Adults treated with an anthracycline plus cyclophosphamide should be offered a four-drug combination: an NK1 receptor antagonist, a 5-HT3 receptor antagonist, dexamethasone, and olanzapine on day 1. Unlike with cisplatin, only olanzapine should be continued on days 2-4.
Olanzapine is an effective antiemetic in a number of settings, Dr. Hesketh said. For example, olanzapine is useful in the setting of hematopoietic stem cell transplant.
A 5-mg dose of olanzapine has proven effective and may be better tolerated than a 10-mg dose.

Moderate-emetic-risk antineoplastic agents

Adults treated with higher-dose carboplatin (area under the curve ≥4 mg/mL per min) should be offered a three-drug combination: an NK1 receptor antagonist, a 5-HT3 receptor antagonist, and dexamethasone on day 1.
Adults treated with moderate-emetic-risk antineoplastic agents (excluding higher-dose carboplatin) should be offered a two-drug combination: a 5-HT3 receptor antagonist and dexamethasone on day 1.
Adults treated with cyclophosphamide, doxorubicin, oxaliplatin, and other moderate-emetic-risk antineoplastic agents known to cause delayed nausea and vomiting may be offered dexamethasone on days 2-3.

Low-emetic-risk antineoplastic agents

Adults treated with low-emetic-risk antineoplastic agents (e.g., fluorouracil, gemcitabine) should be offered a single dose of a 5-HT3 receptor antagonist or a single 8-mg dose of dexamethasone before antineoplastic treatment.

Cannabinoids There is no good data on the use of cannabinoids, apart from those cannabinoids approved by the Food and Drug Administration, according to Dr. Hesketh.

The ASCO guidelines state:

There is insufficient evidence to make a recommendation regarding medical marijuana to prevent nausea and vomiting in cancer patients receiving chemotherapy or radiation.
Similarly, there is insufficient evidence to make a recommendation on the use of medical marijuana in place of the approved cannabinoids dronabinol and nabilone for the treatment of nausea and vomiting in cancer patients receiving chemotherapy or radiation.

SOURCE: Hesketh PJ et al. J Clin Oncol. 2020 Aug 20;38(24):2782-97. https://bit.ly/3oxahUP

Show notes written by Alesha Levenson, MD, a resident at Pennsylvania Hospital, Philadelphia.Disclosures:Dr. Hesketh disclosed institutional research funding from AstraZeneca and F. Hoffmann-La Roche. Dr. Henry has no relevant disclosures.

For information on the negative effects of marijuana, listen to our sister podcast, Psychcast, on MDedge (https://bit.ly/3mBM6TB), Spotify (https://spoti.fi/3mwVvvn), or wherever you get your podcasts.

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Hematology-Oncology News:

National lung cancer screening guidelines may miss younger African American individuals at high risk: https://bit.ly/3e2CmhV
Standard treatment lacking in relapsed / refractory AML: https://bit.ly/3kzoUVh (03:08)
Patients can read your clinical notes starting Nov. 2: https://bit.ly/3mnuudL (05:40)

Update: The deadline for "open notes" has been extended to April 5, 2021.

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In this episode, we review three hematology cases. One case illustrates the work-up and treatment of immune thrombocytopenia (ITP).

Another case demonstrates how to diagnose and manage heparin-induced thrombocytopenia (HIT). And the final case is a patient who presented with anemia, a new mitral valve murmur, and mild splenomegaly.

Host David H. Henry, MD, reviews these cases with three residents from Pennsylvania Hospital in Philadelphia – Sheila De Young, DO; Ronak Mistry, DO; and Debika Shinohara, MD, PhD.

Case 1: Suspected ITP with Sheila De Young, DO

Patient presentation: A 50-year-old female with no past medical history and incidental platelet count of 4,000/microL (normal 150,000-450,000/microL [150-450 x 109/L]).

On physical exam, there was no lymphadenopathy, and the spleen was nonpalpable. She had obvious petechiae on her legs. A urine pregnancy test was negative. Her hemoglobin and white blood cell counts were normal via complete blood count.

ITP definition:
- Acquired thrombocytopenia caused by autoantibodies against platelet antigens.
- One of the most common causes of thrombocytopenia in otherwise asymptomatic adults.
To consider: Increased destruction, decreased production, and pseudothrombocytopenia
- To ensure the platelet count is not falsely low (in the case of pseudothrombocytopenia), looking at a peripheral smear is helpful. If red blood cells and white blood cells appear normal, we can exclude pseudothrombocytopenia.
Work-up:
- We need to rule out secondary causes of thrombocytopenia such as HIV, hepatitis C, chronic lymphocytic leukemia, systemic lupus erythematosus, etc.
Management/treatment:
- In the acute setting, the treatment for ITP is intravenous immunoglobulin and steroids.
- Long-term management of ITP includes steroids, splenectomy, thrombopoietin receptor agonists (romiplostim/eltrombopag), and rituximab.
Case conclusion:
- This patient was found to have ITP. Shared decision-making led to the patient receiving a thrombopoietin receptor.

Case 2: Possible HIT with Ronak Mistry, DO

Patient presentation: A male with ischemic leg and creatinine phosphokinase greater than 4,000 units/L. His platelet count was 101,000/microL on admission, 70,000/microL on the second day, and 60,000/microL on the third day.

The patient was on prophylactic subcutaneous heparin for 48 hours, so the surgery team considered HIT to explain the drop in platelets.

HIT definition:
- A life-threatening complication of exposure to heparin.
- Results from autoantibody directed against endogenous platelet factor 4 (PF4) in complex with heparin.
To consider:
- Determine baseline platelet count, what type of heparin the patient received, and look at when the heparin was administered in relation to when the platelet count dropped.
- HIT is far less common in patients who receive subcutaneous heparin versus intravenous heparin.
- Typically, we see a 50% decrease in platelet count 5-10 days following exposure to heparin.
Work-up:
- In the inpatient setting, it is important to consider other causes that predispose patients to thrombocytopenia (i.e., critical illness, medications).
- Thrombocytopenia can represent a consumptive process of platelets secondary to tissue injury in the setting of elevated creatine phosphokinase.
Diagnosis:
- Enzyme-linked immunosorbent assays (ELISAs) can detect the presence of PF4-heparin antibody.
- ELISA should be followed by a confirmatory test. The serotonin release assay is preferred among diagnostic tests for HIT.
Management/treatment:
- Stop heparin immediately.
- Giving more platelets is not the solution. It increases a person’s risk for thrombotic events.
- The patient needs to be placed on different anticoagulation, such as argatroban or fondaparinux, to carry them through this procoagulant time frame.
Case conclusion:
- HIT was ruled out in this patient.

Case 3: Anemia case with Debika Shinohara, MD, PhD

Patient presentation: A female, age 45 years, with a 4-month history of intermittent fevers and unintentional weight loss.

Her hemoglobin was 8 g/dL, but she had otherwise unremarkable blood work. On physical exam, she was found to have a new mitral valve murmur and mild splenomegaly.

To consider:
- Increased destruction versus decreased production of red blood cells.
- Low reticulocyte count (<5%) suggests decreased production.
Work-up:
- Test vitamin B12, folate, and iron (ferritin, transferrin saturation, and total iron-binding capacity). Elevated transferrin is characteristic of anemia of chronic disease/inflammation.
- Peripheral smear: The red blood cells are normocytic and normochromic in most cases of anemia of inflammation.
- In the setting of elevated transferrin, new-onset murmur, and fever of unknown etiology, it is important to do infectious work-up with blood cultures and cardiac ECG to rule out infective endocarditis.
Infective endocarditis:
- Systemic manifestations include Janeway lesions, Roth spots, and Osler nodes.
- Infection with Streptococcus bovis indicates a need for workup of colon cancer.
Case conclusion:
- Blood cultures came back positive for viridans streptococci.
- The patient was found to have a left atrial myxoma, which was likely the nidus of infection that had seeded the bloodstream.
- The patient was started on intravenous antibiotics and seen by cardiothoracic surgery to remove the myxoma.

Show notes written by Alesha Levenson, MD, a resident at Pennsylvania Hospital.

Disclosures:

All participants in this episode have no relevant financial disclosures.

For more MDedge Podcasts, go to mdedge.com/podcasts

Email the show: podcasts@mdedge.com

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David Henry on Twitter: @davidhenrymd

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Hematology Oncology News:

Study advances personalized treatment for older breast cancer patients (https://bit.ly/3dHieSk)
Delayed cancer screening could cause increase in deaths, study says (https://bit.ly/34afIAS)
Blood group O linked to decreased risk of SARS-CoV-2 infection (https://bit.ly/2T8qilF)

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How do patients with thoracic cancers fare when they develop COVID-19? The researchers behind the TERAVOLT registry are trying to find out.

TERAVOLT investigator Alessio Cortellini, MD, of the University of L’Aquila (Italy), joined host David Henry, MD, to discuss the TERAVOLT registry and its findings, which were recently presented at the European Society for Medical Oncology Virtual Congress 2020.

What is TERAVOLT?

TERAVOLT is an international registry of patients with thoracic cancers and COVID-19 that was launched in March 2020 by Marina Garassino, MD, of the National Cancer Institute of Milan.
The registry enrolls patients with any solid thoracic cancer – small cell and non–small cell lung cancer, mesothelioma, thymic epithelial tumors, and other pulmonary neuroendocrine neoplasms.
Patients are deemed to have COVID-19 if they test positive by reverse transcription–polymerase chain reaction or serology or if they have radiologic or clinical characteristics of COVID-19 and known interaction with a COVID-positive person.
TERAVOLT website: http://teravolt-consortium.org/

TERAVOLT data at ESMO 2020

Data presented at ESMO 2020 included 1,012 patients from 20 countries, mostly in Europe (74%) and North America (23%).
The data encompass patient characteristics, oncologic treatment and COVID-directed therapy, and outcomes.
In all, 32% of patients died of COVID-19.
A multivariable model revealed several factors associated with an increased risk of mortality, including:
- Eastern Cooperative Oncology Group (ECOG) performance status of 2 or greater (odds ratio, 3.6; P < .001)
- Stage IV cancer (OR, 1.9; P < .001)
- Former or current smoker (OR, 1.8; P < .01)
- Prior steroid use (OR, 1.7; P < .01)
- Age 65 years or older (OR, 1.5; P = .01)
- Receiving chemotherapy or no systemic treatment versus immunotherapy, chemoimmunotherapy, or targeted therapy (OR, 1.4; P = .03)
Espinar JB et al. ESMO 2020, Abstract LBA75. https://bit.ly/371aGIJ

A tool to predict mortality

Based on their findings, TERAVOLT researchers developed a nomogram that can help predict mortality in patients with thoracic cancers and COVID-19.
Patients receive points based on ECOG performance status, cancer stage, smoking habits, age, steroid use, and systemic cancer treatment.
- For example, a 70-year-old smoker with an ECOG score of 2 who is receiving third-line treatment with docetaxel for stage IV squamous non–small cell lung cancer would have a score of 260 points, which translates to a greater than 60% risk of death.
- A 50-year-old never-smoker with an ECOG score of 0 who is receiving first-line osimertinib for stage IV non–small cell lung cancer would have a score of 55 points, which translates to a less than 20% risk of death.

Disclosures:

Dr. Cortellini and Dr. Henry have no financial disclosures relevant to this episode.

For more MDedge Podcasts, go to mdedge.com/podcasts

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Hematology-Oncology News:

Radiotherapy planning scans reveal breast cancer patients’ CVD risk (https://bit.ly/2FeoJiH)
FDA OKs combination immunotherapy for first-line mesothelioma treatment (https://bit.ly/2Ff77mS)
Apatinib plus gefitinib: Better PFS but more toxicity (https://bit.ly/34IyVsn)
Atezolizumab strikes out in ovarian cancer (https://bit.ly/3iPjXG1)

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Lorenzo Norris, MD, host of Psychcast, joins Blood & Cancer host David Henry, MD, to discuss steps clinicians can take to alleviate the distress associated with receiving a diagnosis of cancer.

Dr. Norris is director of consult liaison psychiatry at George Washington University, Washington. Dr. Henry is clinical professor of medicine at the University of Pennsylvania, Philadelphia. Both doctors have no disclosures.

A full transcript of this episode is available here:
A conversation on mental health and cancer
https://bit.ly/2Fgat9k

Take-home points

Cancer patients have always been susceptible to developing depression and anxiety after receiving their distressing diagnoses. During the COVID-19 pandemic, the risk for depression and anxiety are even greater because patients face separation from their oncology treatment teams and for some, delays in treatment.
Major depressive disorder (MDD) occurs in up to one-third of cancer patients, and any depressive disorder can be seen in about half.
Another concern is how to screen for depression in the context of cancer. Dr. Norris suggests using the Patient Health Questionnaire–2 (PHQ-2) screener, or the question: “Are you sad or depressed?” Answering those questions can give patients the opportunity to open up about their emotions.
Signs of depression in cancer include nonadherence to treatment, changes in mood and anxiety affecting daily functioning at home or work, and demoralization, which is defined as helplessness, isolation, and despair in the face of overwhelming stressors.

Summary

An emotional upset, such as disbelief, despair, or even denial, might occur immediately after receiving a cancer diagnosis. A depressive disorder, however, is a persistently depressed, sad mood with changes in functioning that affect the patient, his/her family, and even engagement with treatment.
Findings of studies about the prevalence of depression in patients with cancer vary depending on the type of screening and/or diagnostic tool used. In general, the prevalence of MDD is up to 38%, and the prevalence of any depressive disorder is up to 58%. The prevalence of depression is even greater in patients with advanced cancer. In the general population, the 12-month prevalence of MDD is 6%, and the lifetime prevalence is 16%.
It’s useful to think about stress along a continuum of diagnoses ranging from a normal expected stress syndrome, an adjustment disorder, MDD triggered by the event, depression secondary to a general medical condition as can occur in central nervous system and pancreatic cancer, or even a substance-induced mood disorder from either prescribed medications or perhaps a form of coping that has turned maladaptive.
Cognitive-behavioral therapy (CBT) can be explained as examining the way thoughts influence emotions and behavior. When using CBT with cancer patients, a good place to start is checking in on their understanding of their diagnosis, their prognosis, and current and future treatments. The goal is to see whether they have unnecessary cognitive distortions that may be affecting their emotions and behaviors. During periods of extreme stress, CBT can help patients by emphasizing the use of adaptive thoughts, and identifying maladaptive thoughts and behaviors as opportunities for intervention.
To screen for depression, it may be enough to ask: “Are you depressed?” As a screening tool, the PHQ-2 asks only two questions: “Over the last 2 weeks, how often have you been bothered by the following problems: Little interest or pleasure in doing things, or been feeling down, depressed or hopeless? The PHQ-2 score ranges from 1 to 6, and even at the lowest score, it has a sensitivity and specificity of 90.6% and 65.4%, respectively, in detecting any depressive disorder.

References

Krebber AMH et al. Psycho-oncology. 2014 Feb;23(2)121-30.

Walker J et al. Ann Oncol. 2013 Apr 1;24(4):895-900.

Trinidad AC et al. Psychiatr Ann. 2011;4(9):439-42.

Daniels S. J Adv Pract Oncol. 2015 Jan-Feb;6(1):54-6.

Other resources

PHQ-2: https://www.hiv.uw.edu/page/mental-health-screening/phq-2

National Cancer Institute: Depression–Health Professional Version: https://www.cancer.gov/about-cancer/coping/feelings/depression-hp-pdq

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Hematology-Oncology News:

Divergent findings with paclitaxel and nab-paclitaxel in TNBC (https://bit.ly/33vemjS)
Palbociclib plus letrozole improves PFS in advanced endometrial cancer (https://bit.ly/2GIUl08)
Global stomach cancer deaths decline as colorectal cancer deaths stagnate, rise (https://bit.ly/33zBVs1)

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There were a number of practice-changing and ground-breaking studies presented at the ESMO 2020 Virtual Congress, according to our guest in this episode.

Alan P. Lyss, MD, subprincipal investigator for Heartland Cancer Research NCORP, joined host David H. Henry, MD, to review highlights from ESMO 2020.

The pair discussed studies on gynecologic, breast, lung, gastrointestinal, and genitourinary cancers, as well as studies of anemia and COVID-19 in cancer patients.

COVID-19 and cancerLBA77: Anti-SARS-CoV-2 antibody response in patients with cancer and oncology healthcare workers: A multicenter, prospective study. https://bit.ly/3cNNkar

This study suggests SARS-CoV-2-specific IgG antibody response is not different between cancer patients (n = 61) and subjects without cancer (n = 105).
Overall, 83.8% of subjects were IgG-positive, and there was no significant difference in IgG positivity between the cancer patients and the health care workers (P = .39).

LBA83: Outcomes of the 2019 novel coronavirus in patients with or without a history of cancer: A multi-centre North London experience. https://bit.ly/2EJMpv4

This study suggests COVID-19 patients with a history of cancer may have a similar risk of death as COVID patients without a history of cancer, with exceptions.
The odds ratio for mortality, comparing the cancer patients (n = 30) to the non-cancer patients (n = 90), was 1.05.
The odds ratio for mortality was 4.05 for cancer patients who had received systemic therapy in the prior 28 days.

Lung cancer: RadiotherapyLBA3_PR: An international randomized trial, comparing post-operative conformal radiotherapy (PORT) to no PORT, in patients with completely resected non-small cell lung cancer (NSCLC) and mediastinal N2 involvement: Primary end-point analysis of LungART (IFCT-0503, UK NCRI, SAKK) NCT00410683. https://bit.ly/3jtojUo

This study enrolled 501 patients with completely resected NSCLC and mediastinal N2 involvement, and they were randomized to PORT or no PORT.
There was no significant between-arm difference in disease-free survival (DFS) or overall survival (OS).
The 3-year DFS rate was 47.1% with PORT and 43.8% with no PORT. The 3-year OS rate was 66.5% and 68.5%, respectively.
These results suggest conformal PORT should not be standard care in all completely resected N2 NSCLC patients, according to Dr. Lyss. “This may have been the most obviously and immediately practice-changing study among those I heard presented,” he said.

Endometrial cancerLBA28: A randomised double-blind placebo-controlled phase II trial of palbociclib combined with letrozole (L) in patients (pts) with oestrogen receptor-positive (ER+) advanced/recurrent endometrial cancer (EC): NSGO-PALEO / ENGOT-EN3 trial. https://bit.ly/2SanTX1

This study enrolled 77 patients with ER+ advanced or recurrent endometrial cancer, and they were randomized to palbociclib plus letrozole or placebo plus letrozole.
The median progression-free survival (PFS) was 8.3 months in the palbociclib arm and 3 months in the control arm.
Dr. Lyss called this a “small” but “important” study. He and Dr. Henry agreed that a confirmatory study is needed.

Breast cancerLBA5_PR: Abemaciclib in high risk early breast cancer. https://bit.ly/3igxbvw

This trial enrolled 5,637 women with hormone receptor-positive, HER2/neu oncogene-negative, early breast cancer.
They were randomized to receive standard endocrine therapy (ET) alone or standard ET with abemaciclib.
The 2-year invasive DFS rate was 92.2% with abemaciclib and 88.7% with ET alone (hazard ratio, 0.747; P = .0096).
Dr. Lyss said these data suggest abemaciclib could have “the potential to save many thousands of lives.”
However, he noted that 16% of patients discontinued abemaciclib prematurely due to adverse events, and more than 300 of the 463 patients who stopped abemaciclib also stopped ET – a “disaster,” according to Dr. Lyss.

LBA12: PALLAS: A randomized phase III trial of adjuvant palbociclib with endocrine therapy versus endocrine therapy alone for HR+/HER2- early breast cancer. https://bit.ly/2GbuluE

This trial enrolled 5,760 patients with hormone receptor-positive/HER2-negative early stage breast cancer. They were randomized to palbociclib plus ET or ET alone.
Results from this trial run counter to results from the abemaciclib trial, in that adding palbociclib to ET did not improve invasive DFS.
The 3-year invasive DFS rate was 88.2% in the palbociclib arm and 88.5% in the ET-alone arm (HR, 0.93).
Dr. Lyss said he can see no explanation for the different results with abemaciclib and palbociclib, but longer follow-up and analyses of biospecimens may shed some light.

LBA17: ASCENT: A randomized phase III study of sacituzumab govitecan (SG) vs treatment of physician’s choice (TPC) in patients (pts) with previously treated metastatic triple-negative breast cancer (mTNBC). https://bit.ly/3ilHwGd

The study enrolled 529 patients with relapsed/refractory metastatic TNBC.
They were randomized to SG or single-agent physician’s choice of therapy (capecitabine, eribulin, vinorelbine, or gemcitabine).
SG outperformed physician's choice. The median PFS was 5.6 months with SG and 1.7 months with physician’s choice. The median OS was 12.1 months and 6.7 months, respectively.

LBA16: IMpassion130: Final OS analysis from the pivotal phase III study of atezolizumab + nab-paclitaxel vs placebo + nab-paclitaxel in previously untreated locally advanced or metastatic triple-negative breast cancer. https://bit.ly/33fYYb7

This trial enrolled 902 patients with locally advanced or metastatic TNBC.
They were randomized to first-line nab-paclitaxel plus placebo or nab-paclitaxel plus atezolizumab.
The median OS was 21 months in the atezolizumab arm and 18.7 months in the control arm (HR, 0.87, P = .0770).
The 3-year OS in PD-L1-positive patients was 36% and 22%, respectively. “I think anybody would choose the combination with atezolizumab with a difference like that,” Dr. Lyss said.

LBA15: Primary results from IMpassion131, a double-blind placebo-controlled randomised phase III trial of first-line paclitaxel (PAC) ± atezolizumab (atezo) for unresectable locally advanced/metastatic triple-negative breast cancer (mTNBC). https://bit.ly/36iEoIS

This trial enrolled 651 patients with locally advanced or metastatic TNBC.
They were randomized to first-line paclitaxel plus placebo or paclitaxel plus atezolizumab.
Dr. Lyss noted that, unlike IMpassion130, the results of IMpassion131 were “completely negative.”
In the PD-L1-positive population, the median PFS was 5.7 months in the placebo arm and 6.0 months in the atezolizumab arm (HR, 0.82; P = .20).
In the overall population, the median PFS was 5.6 months and 5.7 months, respectively (HR, 0.86).
It’s unclear why results from IMpassion130 and IMpassion131 differ, Dr. Henry noted. Steroid use, study design, or chance might all play a role, according to a discussant at ESMO.

Urothelial cancerLBA24: TROPHY-U-01 cohort 1 final results: A phase II study of sacituzumab govitecan (SG) in metastatic urothelial cancer (mUC) that has progressed after platinum (PLT) and checkpoint inhibitors (CPI). https://bit.ly/3kYvq7R

This study enrolled 113 patients with unresectable locally advanced or metastatic urothelial cancer. All patients received SG.
The overall response rate was 27% in the overall population and 25% in patients with liver metastasis.
The median PFS was 5.4 months, and the median OS was 10.5 months.
Dr. Henry said the response and survival data were “rather impressive,” and Dr. Lyss noted that biomarker studies might allow for better selection of patients who should receive SG.

Gastrointestinal cancerLBA6_PR: Nivolumab (nivo) plus chemotherapy (chemo) versus chemo as first-line (1L) treatment for advanced gastric cancer/gastroesophageal junction cancer (GC/GEJC)/esophageal adenocarcinoma (EAC): First results of the CheckMate 649 study. https://bit.ly/2GcOroj

This study enrolled 1,581 patients with GC, GEJC, or EAC, and 60% of patients were PD-L1-positive with a combined positive score (CPS) of at least 5.
Patients were randomized to first-line treatment with nivolumab plus chemotherapy or chemotherapy alone (XELOX or FOLFOX).
In patients with PD-L1 CPS ≥ 5, the median OS was 14.4 months in the nivolumab arm and 11.1 months in the chemotherapy arm (HR, 0.71; P < .0001).
The median PFS was 7.7 months and 6.2 months, respectively (HR, 0.68; P < .0001).
Dr. Lyss noted that using checkpoint inhibitors in the frontline or even adjuvant setting appears beneficial in this patient population, as demonstrated by additional trials presented at ESMO 2020:
- LBA7_PR (https://bit.ly/2GfXW65)
- LBA8_PR (https://bit.ly/3kYokQM)
- LBA9_PR (https://bit.ly/3ikBaaa).

Lung cancer: Checkpoint inhibitorsDr. Henry briefly discussed three abstracts on checkpoint inhibitors in NSCLC — LBA51, LBA52, and LBA53.

LBA51: KEYNOTE-024 5-year OS update: First-line (1L) pembrolizumab (pembro) vs platinum-based chemotherapy (chemo) in patients (pts) with metastatic NSCLC and PD-L1 tumour proportion score (TPS) ≥50%. https://bit.ly/2ELdNsE

The 5-year OS rate was 31.9% with pembrolizumab and 16.3% with chemotherapy (HR, 0.62).

LBA52: EMPOWER-Lung 1: Phase III first-line (1L) cemiplimab monotherapy vs platinum-doublet chemotherapy (chemo) in advanced non-small cell lung cancer (NSCLC) with programmed cell death-ligand 1 (PD-L1) ≥50%. https://bit.ly/3jjSiy9

The median OS was 22.1 months in the cemiplimab arm and 14.3 months in the chemotherapy arm (P = .002).

LBA53: Precision immuno-oncology for advanced non-small cell lung cancer (NSCLC) patients (pts) treated with PD1/L1 immune checkpoint inhibitors (ICIs): A first analysis of the PIONeeR study. https://bit.ly/2GbjhO0

This study revealed biomarkers that might help guide treatment with immune checkpoint inhibitors.

Renal cell carcinoma696O_PR: Nivolumab + cabozantinib vs sunitinib in first-line treatment for advanced renal cell carcinoma: First results from the randomized phase III CheckMate 9ER trial. https://bit.ly/30lEMmg

This study enrolled 651 patients with previously untreated metastatic renal cancer.
They were randomized to cabozantinib plus nivolumab or sunitinib.
The median PFS was 16.6 months with the combination and 8.3 months with sunitinib.
The median OS was improved with the combination as well (HR, 0.61).
Dr. Lyss said these results support the use of nivolumab plus cabozantinib in this patient population. However, he also expressed reservations related to tolerability, quality of life, eligibility criteria, and short follow-up.

Anemia1822P: Impact of iron-deficiency management on quality of life in cancer patients: A prospective cohort study (CAMARA study). https://bit.ly/2Sf1TdE

This study enrolled 248 patients with solid tumors, including 74.5% with absolute iron deficiency (transferrin saturation coefficient < 20%) and 191 with anemia.
Patients were treated with intravenous iron, and their quality of life (FACT-An scores) improved significantly between study enrollment and each assessment.
Dr. Henry said the take-home message is that clinicians shouldn’t miss anemia or iron deficiency, and they shouldn’t transfuse patients automatically but, instead, consider iron supplementation.

Disclosures:

Dr. Henry has no financial disclosures relevant to this episode.

Dr. Lyss writes a column for MDedge Hematology/Oncology called Clinical Insights. He has no other conflicts of interest.

For more MDedge Podcasts, go to mdedge.com/podcasts

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David Henry on Twitter: @davidhenrymd

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Hematology-Oncology News:

No benefit with postoperative radiotherapy in stage IIIA2 NSCLC (https://bit.ly/3i1196r)
First-in-class ADC ups survival in mTNBC (https://bit.ly/2GaoVQ2)
Sotorasib is a 'triumph of drug discovery' in cancer (https://bit.ly/2FQwpIt)
TKI choice key for fit/unfit patients with Ph+ALL (https://bit.ly/3kLdmOs)

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How do patients fare when they have cancer and COVID-19? Researchers developed the COVID-19 and Cancer Consortium (CCC19) and the National Cancer Institute COVID-19 in Cancer Patients Study (NCCAPS) to gain some insight.

In this episode, Brian Rini, MD, a professor of medicine at Vanderbilt University Medical Center, Nashville, Tenn., and host of The Uromigos podcast, explains what CCC19 and NCCAPS are. He also discusses findings from CCC19 that were presented at the European Society of Medical Oncology Virtual Congress 2020.

NCCAPS (NCT04387656)

NCCAPS is a natural history study of COVID-19 in patients with active cancer.
It is a prospective study, funded by the National Cancer Institute, that is open at more than 500 centers.
The study is open to U.S. adults who are receiving active cancer treatment and either have COVID-19 or are awaiting a SARS-CoV-2 test result.
Researchers collect blood samples and other data from patients enrolled.
- Blood is collected at baseline and at regular intervals incorporated into patients’ normal oncology follow-up.
- The samples will be used to assess things like genomics, cytokine abnormalities, and coagulation parameters.
No data from NCCAPS have been released to date, but more than 100 patients have been enrolled.
For more information, visit the NCCAPS webpage: https://bit.ly/3ck8nBb.

CCC19 (NCT04354701)

CCC19 is a retrospective database that includes information on patients with active cancer or a history of cancer who have been diagnosed with COVID-19, with or without a confirmatory test.
Health care providers or their proxies from the United States, European Union, Argentina, Canada, Mexico, and United Kingdom can report cases through the CCC19 website.
All data are deidentified.
More than 100 institutions are now part of CCC19.
Data from CCC19 were presented in two abstracts at ESMO 2020:
- Wise-Draper TM et al. Abstract LBA71. https://bit.ly/3iUarm2
- Grivas P et al. Abstract LBA72. https://bit.ly/33OKttP
The data from LBA72, which includes nearly 4,000 patients, suggest cancer-specific factors are associated with a greater risk of 30-day all-cause mortality, including:
- Progressive cancer (adjusted odds ratio, 2.9).
- Hematologic malignancy (aOR, 1.7).
- Receiving cancer therapy within the past 3 months (aOR, 1.2).
It still isn’t clear if certain cancer treatments increase the risk of mortality, Dr. Rini said, but researchers are investigating that.
For more information on CCC19, visit https://ccc19.org/.

Disclosures:

Dr. Rini and Dr. Henry have no relevant conflicts of interest.

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This week in Hematology and Oncology news:

Large waistline linked to higher risk of prostate cancer death (https://bit.ly/3iRxmya)
FOLFOXRI tops doublets as bevacizumab backbone for mCRC (https://bit.ly/32QpTKi)
AI algorithm on par with radiologists as mammogram reader (https://bit.ly/35WnAXV)
How I Treat: For low-risk MDS, treat 'what bugs patients most' (https://bit.ly/2ZU5TEU)

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How has COVID-19 impacted medical students? Two students from Royal College of Surgeons in Ireland (RCSI), Dublin, describe their experiences in this episode.

Evani Patel and Sarah Chen, both second-year medical students at RCSI, tell host David H. Henry, MD, how the COVID-19 pandemic has shaped their educational experience thus far.

Now, the pandemic has shifted the students’ education to a mix of virtual and in-person learning at RCSI, but COVID-19 also impacted the pair’s summer studentships at University of Pennsylvania, Philadelphia.

Typically, the studentships involve seeing patients, attending lectures, and completing projects. This year, however, the students were unable to travel to Philadelphia in person, so they completed their projects and attended lectures virtually.

Disclosures:

Ms. Chen, Ms. Patel, and Dr. Henry have no disclosures relevant to this episode.

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Hematology/Oncology News:

Study supports multigene panel testing for all breast cancer patients with second primary cancers: https://bit.ly/3m6RyOG
Source: https://bit.ly/2ZKXund
Atezolizumab TNBC indication ‘in jeopardy’ because of phase 3 results: https://bit.ly/35rqzrl
Alert: https://bit.ly/2Reh1HM
Trial: https://bit.ly/2ZqqIqX
Pralsetinib: Second drug for RET+ NSCLC approved in U.S.: https://bit.ly/3bTdGaz
Unexpected results in new COVID-19 ‘cytokine storm’ data: https://bit.ly/3k8fIGL
JAMA research letter: https://bit.ly/35ubxB4

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Treatment strategies for myelodysplastic syndromes (MDS) vary widely depending upon patients’ prognosis. In this episode, Shannon R. McCurdy, MD, of the University of Pennsylvania, Philadelphia, joined host David H. Henry, MD, to discuss how she treats patients with MDS.

To start, Dr. McCurdy evaluates patients using the revised International Prognostic Survival Scale (IPSS-R), which can predict the aggressiveness of MDS.

Low IPSS-R scores (<1.5) are associated with low-risk MDS, which has a median survival of 8.8 years.
High IPSS-R scores (>6) are associated with high-risk MDS, which has a median survival of 0.8 years.

Dr. McCurdy also performs molecular testing to assess risk. A poor-risk molecular profile can increase the IPSS-R by 1 point, she said.

Dr. McCurdy went on to explain how she approaches treatment according to risk.

Asymptomatic, low-risk MDS

Monitor patients’ complete blood count, typically every 3-6 months, and intervene if there is progression.

Low-risk patients who require treatment

Those who have deletion 5q with anemia should receive lenalidomide first.
Patients without 5q deletion and low erythropoietin levels (<500 mU/mL) should receive an erythropoietin-stimulating agent (ESA), such as darbepoetin alfa.
In patients with loss of response to an ESA, add lenalidomide or granulocyte colony–stimulating factor to ESA treatment.
Patients who fail ESA treatment should receive luspatercept.
Patients with thrombocytopenia should receive a thrombopoietin mimetic, such as eltrombopag, as a single agent.

Intermediate-, high-, or very-high-risk patients

Allogeneic bone marrow transplant is usually done in patients who are aged 75 years or younger, are fit, and want aggressive treatment, Dr. McCurdy said.
In patients not eligible for transplant, start a hypomethylating agent (HMA), such as azacitidine, and continue as long as the patients respond.
In patients not eligible for transplant who progress on an HMA, consider adding venetoclax.
- Dr. McCurdy said she doesn’t add venetoclax to an HMA up front because it can reduce patients’ quality of life, but a study presented at ASH 2019 showed high response rates with venetoclax and an HMA in combination (Blood. 2019; 134 [supplement 1]: 4241).

Drugs under investigation

Roxadustat, an oral inhibitor of hypoxia-inducible factor, is under investigation in a phase 3 trial of patients with lower-risk MDS (NCT03263091).
Dr. McCurdy is involved in a phase 3 trial of magrolimab, with or without azacitidine, in higher-risk patients with MDS (NCT04313881).

Disclosures:

Dr. McCurdy and Dr. Henry have no financial disclosures relevant to this episode.

Show notes by Marianne Riordan, MD, resident at Pennsylvania Hospital, Philadelphia.

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Blood & Cancer News: * Delaying RT for higher-risk prostate cancer found safe: https://bit.ly/2F1cKoQ
Source: https://bit.ly/2FaaMCr
RTOG 9413: https://bit.ly/2DL2FM4
RTOG 9910: https://bit.ly/2F8itJe * HOME-PE trial clarifies which pulmonary embolism patients to treat at home: https://bit.ly/3ibNTN9 * Melanoma experts say ‘no’ to routine gene profile testing: https://bit.ly/2Zka10p
Source: https://bit.ly/2ZkzerB * VTE, sepsis risk increased among COVID-19 patients with cancer: https://bit.ly/2DL2Wi4

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Episode 94 features the best of ASCO 2020, and we'll see you all with new content for episodes 95 and 96.

Best of:

How did it go? Nick Andrews and David Henry, MD, discuss how Dr. Henry thought the meeting went from episode 73.
Top five abstracts. Dr. Henry and Alan Lyss, MD, discuss their top five abstracts each from episode 74.
Preview/review. Howard "Skip" Burris, III, MD, joined Dr. Henry to talk about how ASCO was changing amid the COVID-19 pandemic from episode 68.

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MDedge Hematology-Oncology news for the first week of September 2020.

Aspirin may accelerate cancer progression in older adults: https://bit.ly/2ENHRUc
ASPREE trial: https://bit.ly/2QAsMYW
Meta-analysis: https://bit.ly/2D6rXnl
AsCaP: https://bit.ly/2G06X2I
Black/White gap gone: ‘The only cancer where this has happened’: https://bit.ly/3jm8PBm
Source: https://bit.ly/3lv4u0m
Selpercatinib 'poised to alter the landscape' of RET+ cancers: https://bit.ly/34PYSbs
Lung cancer results: https://bit.ly/3gB1FY7
Thyroid cancer results: https://bit.ly/2EHhCz5
Study confirms it's possible to get COVID-19 twice: https://bit.ly/3bd4wWg

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The SECURE-SCD registry was designed to collect and disseminate information on patients with sickle cell disease (SCD) who develop COVID-19.

Two of the registry’s organizers are Amanda Brandow, DO, and Julie Panepinto, MD, both of the Medical College of Wisconsin/Children’s Wisconsin in Milwaukee.

In this episode, Dr. Brandow and Dr. Panepinto discuss SECURE-SCD and its findings with host David H. Henry, MD.

SECURE-SCD is an online registry that was launched in March 2020. On the registry’s website (https://covidsicklecell.org/), health care providers can submit deidentified data on patients with COVID-19 and SCD.

The submitted data are then published on the website. Updates are made regularly, usually every Friday. The following information from SECURE-SCD was current as of recording this episode.

SECURE-SCD includes data on nearly 300 SCD patients with COVID-19.
Eight countries and more than 25 U.S. states are represented in the registry.
The average patient age is 25.5 years, with the largest population clustered around ages 18-30 years.
The most common presenting symptom is pain, which has been reported in more than half of patients.
About a third of patients presented with pneumonia and/or acute chest syndrome.
Stroke has been relatively uncommon in the population.
Three cases of thrombosis have been reported. However, information on thrombosis was not collected initially, so cases may be higher.

For more details, see the recent publication of SECURE-SCD data: Panepinto JA et al. Coronavirus disease among persons with sickle cell disease, United States, March 20–May 21, 2020. Emerg Infect Dis. 2020 Oct. doi: 10.3201/eid2610.202792.

To view the latest data, visit https://covidsicklecell.org/updates-data/.

Disclosures:

Dr. Brandow, Dr. Panepinto, and Dr. Henry have no financial disclosures relevant to this episode.

Show notes by Sheila De Young, DO, resident at Pennsylvania Hospital, Philadelphia.

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News for the week of August 24, 2020.

Beyond baseline, DBT no better than mammography for dense breasts: https://bit.ly/2FTRnpp
Study source: https://bit.ly/2FTLkkI
Lead author: https://bit.ly/3graAv0
Subgroups predict adjuvant chemoradiotherapy benefits in low-grade glioma: https://bit.ly/31oHkkr
Source: https://bit.ly/3aSVe1j
Diabetes plus weight loss equals increased risk of pancreatic cancer: https://bit.ly/2Etmbws
Source: https://bit.ly/2EyRBkV

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Dr. David Henry welcomes NBA power forward Mason Plumlee. Plumlee, who is now participating in the NBA's controlled COVID-19 environment, affectionately referred to as the "bubble," tested positive for COVID-19 before we knew that loss of taste and smell was a symptom.

In a wellness and intellectual change-of-pace episode, Plumlee joins Dr. Henry to talk about his background in medicine and biology, his experiences in the NBA bubble, and his time playing for Duke University.

Mason Plumlee on Twitter: @masonplumlee https://bit.ly/2FBSQ3r

David Henry on Twitter: @DavidHenryMD http://bit.ly/2HXI6Lw

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Hematology-Oncology news:

Chemo-free management of mesothelioma on horizon: https://bit.ly/2CyL6xY
CheckMate 743: https://bit.ly/2CBy6HX
INITIATE trial: https://bit.ly/3axxdg8
MAPS2: https://bit.ly/32hWCa0
FDA approves first liquid biopsy/NGS test for lung cancer: https://bit.ly/3258jRn
Swallowable 'sponge on a string' to diagnose esophageal cancer: https://bit.ly/3iUbLFb
Source: https://bit.ly/2Q0T6en
COVID-19 impact: Less chemo, immune checkpoint inhibitors, and steroids: https://bit.ly/2Ebwmpq
Survey: https://bit.ly/3h14S4h

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Hanny Al-Samkari, MD, joins the podcast to discuss thrombosis in COVID-19 and lung cancer patients as well as the use of bevacizumab in patients with hereditary hemorrhagic telangiectasia (HHT).

Dr. Al-Samkari, of Massachusetts General Hospital, presented three studies on these topics at the virtual ISTH 2020 Congress. In this episode, Dr. Al-Samkari describes these studies to host David H. Henry, MD.

Thrombosis, Bleeding, and the Effect of Anticoagulation on Survival in Critically Ill Patients with COVID-19 in the United States
This 67-center study included 3,239 critically ill adults with COVID-19.
The 14-day incidence of radiographically confirmed venous thromboembolism (VTE) was 6.3%.
The 14-day incidence of strictly defined major bleeding was 2.8%.
Patients who received therapeutic anticoagulation in the first 2 days of ICU admission had a similar risk of death at 28 days as patients who did not receive anticoagulation.

Al-Samkari H et al. ISTH 2020, Abstract LB/CO01.2. https://bit.ly/3alvquE.

An International Multicenter Study of Bevacizumab for Bleeding in Hereditary Hemorrhagic Telangiectasia — The InHIBIT-Bleed Study
This 12-center trial included 238 patients with HHT.
Patients received bevacizumab for a median of 12 months (range, 1-96 months).
The most common dosing schedule was 5 mg/kg every 2-4 weeks for four to six treatments of induction, followed by maintenance.
During the first year, bevacizumab increased the mean hemoglobin by 3.2 g/dL.
At 6 months post treatment, transfusions of red blood cells had decreased by 82% and iron infusions had decreased by 70%.

Al-Samkari H et al. ISTH 2020, Abstract OC 9.2. https://bit.ly/30L5PrV.

The ALK Rearrangement is a Major Risk Factor for Venous and Arterial Thrombosis in Non–Small Cell Lung Cancer
This retrospective study included patients with advanced non–small cell lung cancer (NSCLC).
There were 422 patients with ALK-rearranged NSCLC and 385 with non–ALK-rearranged NSCLC.
The rate of initial VTE was 42.7% in ALK and 28.6% in non-ALK NSCLC.
The rate of recurrent VTE was 13.5% in ALK and 3.1% in non-ALK NSCLC.
Arterial thrombosis rates were similar in ALK and non-ALK NSCLC (5.0% and 4.4%, respectively).
In analyses controlling for time and thrombosis risk factors, the risk of VTE was three times higher and the risk of arterial thrombosis was four times higher among patients with ALK rearrangement.

Al-Samkari H et al. ISTH 2020, Abstract OC 10.2. https://bit.ly/30KHouB.

Disclosures:

Dr. Al-Samkari has no relevant disclosures.

Dr. Henry has no relevant disclosures.

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This week in HemOnc news:

Study: Immune checkpoint inhibitors don't increase risk of death in cancer patients with COVID-19: https://bit.ly/2PEttQa
System provides 'faster, less invasive' method for breast cancer detection: https://bit.ly/3achral
Source: https://bit.ly/3gN507j
FDA approves belantamab in relapsed/refractory multiple myeloma: https://bit.ly/3ksQtQu
FDA approves new drug for diffuse large B-cell lymphoma: https://bit.ly/3kvoIXn

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How does the community oncologist treat multiple myeloma? Gustavo A. Fonseca, MD, of Florida Cancer Specialists, shares his approach to myeloma treatment with host David H. Henry, MD.

At the start of this episode, Dr. Fonseca and Dr. Henry discuss their love of podcasts, mentioning shows that have proven useful to them personally and professionally.

The pair then move on to discuss hypothetical myeloma cases and advances in treatment. They cover triple-agent therapy, transplant, and bone-modifying agents. They also discuss the management of anemia, what to do after treatment failure, and how far myeloma treatment has come in recent years.

Disclosures:

Dr. Fonseca and Dr. Henry have no financial disclosures relevant to this episode.

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This week in HemOnc News:

Higher death rate seen in cancer patients with nosocomial COVID-19
Article: https://bit.ly/2XjRLDq
Source: https://bit.ly/3goLGgF
Robotic renal surgery bests open partial nephrectomy
Article: https://bit.ly/2PhHS4M
Source: https://bit.ly/3gqXXBd
Large cohort study: Bevacizumab safe, effective for severe HHT bleeds
Article: https://bit.ly/2XpuZdj
Source: https://bit.ly/2BXHVQg

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COVID-19 can have a negative impact on systems throughout the body, beyond just the lungs, according to a review published in Nature Medicine. Two authors of the review joined host David H. Henry, MD, to discuss their article, “Extrapulmonary manifestations of COVID-19.”

Aakriti Gupta, MD, of Columbia University Irving Medical Center, and Kartik Sehgal, MD, of Dana Farber Cancer Institute, discussed:

ACE2, the entry receptor for SARS-CoV-2
Neurologic and gastrointestinal manifestations of COVID-19
Mechanisms of coagulation and thromboprophylaxis
COVID-19 in cancer patients
The impact of quarantine on cardiology patients
The lasting effects of COVID-19 and the need for follow-up
The importance of international collaboration for clinical trials.

For more details on how COVID-19 can affect the body, see the full review in Nature Medicine:

Gupta A. et al. Nat Med. 2020 Jul;26(7):1017-1032.

Disclosures:

Dr. Henry and Dr. Sehgal have no financial disclosures relevant to this episode.

Dr. Gupta disclosed relationships with the Arnold & Porter Law Firm for work related to the Sanofi clopidogrel litigation, the Ben C. Martin Law Firm for work related to the Cook inferior vena cava filter litigation, Edward Lifesciences, and Heartbeat Health.

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This week in HemOnc News:

PSMA PET/CT may be new 'gold standard' for prostate cancer staging
Source: https://bit.ly/2CRaq2t
Study: https://bit.ly/3f18YHL
Analysis of early-onset cancer suggests need for genetic testing
Source: https://bit.ly/2WZSIR3
AACR Abstract: https://bit.ly/3f18YHL
Early screening may halve breast cancer mortality in childhood cancer survivors
Source: https://bit.ly/2WZSIR3
Study: https://bit.ly/39DoJUf
COVID-19: Heavy toll from ongoing cancer referral delays Source: https://bit.ly/3g6DiSF
First study: https://bit.ly/2WZSVnj
Second study: https://bit.ly/30375Gp

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While relaxing on the Jersey Shore, host and MDedge Hematology/Oncology Editor-in-Chief, David Henry, MD, dove into the July 10, 2020, issue of the Journal of Clinical Oncology. In episode 82, we do the same.

J Clin Oncol. 2020 Jul 10. 38(20). 2217-2361. (https://bit.ly/2ZQEJ27)

You can follow along with the following articles:

Lumpectomy Margins for Invasive Breast Cancer and Ductal Carcinoma in Situ: Current Guideline Recommendations, Their Implications, and Impact (https://bit.ly/39m5P3W)
Accelerated Partial Breast Irradiation and Intraoperative Partial Breast Irradiation: Reducing the Burden of Effective Breast Conservation (https://bit.ly/2Bm9McB)
Partial Breast Irradiation Is the Preferred Standard of Care for a Majority of Women With Early‐Stage Breast Cancer (https://bit.ly/3jqAxhj)
Whole-Breast Irradiation Is the Preferred Standard of Care for the Majority of Patients With Early-Stage Breast Cancer (https://bit.ly/3jwRma3)
Regional Nodal Management in Patients With Clinically Node-Negative Breast Cancer Undergoing Upfront Surgery (https://bit.ly/2WI8Syj)
Locoregional Management After Neoadjuvant Chemotherapy (https://bit.ly/2OOjRCc)

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The latest news from MDedge Hematology/Oncology:

In this episode:

MRI reliably identifies significant prostate cancer
Original MDedge article (https://bit.ly/3hgKT1h)
PROMIS analysis (https://bit.ly/3fLOiEN)
Drug-drug interactions to avoid in patients with GI cancer
Original MDedge article (https://bit.ly/39eHi0G)
ctDNA clearance tracks with PFS in NSCLC subtype
Original MDedge article (https://bit.ly/3eJKm6o)
Abstract from AACR 2020 (https://bit.ly/30uQQ3R)
TATTON results in The Lancet Oncology (https://bit.ly/3jq1L7J)
COVID-19 symptoms can linger for months
Original MDedge article (https://bit.ly/3eNREG0)
JAMA research letter (https://bit.ly/2WFS3UW)

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Cancer patients often ask what they should eat, but it’s just as important to know when they should eat, according to Dawn Lemanne, MD, of Oregon Integrative Oncology, Ashland, and the University of Arizona, Tucson.

Dr. Lemanne tells host David H. Henry, MD, how cancer patients may benefit from fasting. The pair discuss immune system suppression, insulinlike growth factor I (IGF-I), and blood glucose monitoring.

Fasting and the immune system

Fasting before and after chemotherapy can put part of the immune system “to sleep,” thereby protecting it from the deleterious effects of treatment, Dr. Lemanne says.
A study of patients on platinum-based chemotherapy suggested that fasting for at least 48 hours (divided pre- and post chemo) led to decreased DNA damage in leukocytes (BMC Cancer. 2016 Jun 10;16:360).
Based on this study and preclinical results, Dr. Lemanne advises fasting in patients receiving emetogenic and immunosuppressive chemotherapies.
Lemanne defines fasting as consuming no (or few) calories. Patients can drink water and caffeinated beverages such as coffee or tea, but the drinks can’t include additions like cream or sugar.

IGF-I levels

Several studies have linked the growth hormone IGF-I to cancer (Endocrinol Metab Clin North Am. 2012;41[2]:335-50).
Lemanne says high IGF-I levels in middle age seem to increase the risk of cancer, and high IGF-I levels in patients who already have cancer may increase the risk of death.
Overnight intermittent fasting of 13 hours or more can lower IGF-I levels, according to Dr. Lemanne.
Although there are drugs that can lower IGF-I levels, Dr. Lemanne doesn’t recommend them because of potential side effects.

Blood sugar

Studies have suggested that metformin can improve survival in diabetics with cancer (Cancer Manag Res. 2019;11:3295-313).
Researchers are investigating whether metformin provides the same survival benefit to nondiabetics with cancer.
Lemanne says she checks cancer patients’ hemoglobin A1C and fasting insulin levels even if they are not diabetic. She even gives patients glucose monitoring systems so they can see how their blood sugar spikes after meals.
If a patient’s blood sugar levels are high, Dr. Lemanne will try to lower them via dietary changes. If that doesn’t work, she will give patients low-dose metformin.

Disclosures:

Dr. Lemanne and Dr. Henry have no relevant disclosures.

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The latest news for hematology and oncology professionals.

In this episode:

USPSTF: Earlier lung cancer screening can double eligibility
Review and comment on the USPSTF site: https://bit.ly/3fppiD7
National Lung Screening Trial https://bit.ly/2CvNRQt
Lifestyle choices may reduce breast cancer risk regardless of genetics
Read the article on MDedge: https://bit.ly/2ZrsWqN
Read the original research: https://bit.ly/3etRLGx (JAMA Netw Open. 2020;3(4):e203760).
FDA approves oral therapy for myelodysplastic syndromes, CMML
Read the FDA news release: https://bit.ly/2WeUIVb
Commentary: 'Doc, Can I Get a Mask Exemption?'
Read the full commentary from Dr. Rizzo: https://wb.md/2Wfoh9i
Read the CDC Recommendations: https://bit.ly/304OTed
Read more about Dr. Albert Rizzo: https://bit.ly/3j2QDgW

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Oncologist Don S. Dizon, MD, joins the podcast to discuss how the COVID-19 pandemic has affected him personally and professionally. Dr. Dizon is the director of women’s cancers at Lifespan Cancer Institute and director of medical oncology at Rhode Island Hospital, both in Providence.

Dr. Dizon tells host David H. Henry, MD, how COVID-19 affected his patients, colleagues, and research as well as his personal life. Dr. Dizon chronicled some of these developments in a series of columns published on Medscape.

Disclosures:

Dr. Dizon has relationships with Regeneron, Astra-Zeneca, Clovis, Bristol-Myers Squibb, and Kazia. He is a columnist for Medscape, which is owned by the same parent company as MDedge News.

Dr. Henry has no relevant disclosures.

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Ilana Yurkiewicz, MD, recorded dozens of Clinical Correlation segments for Blood & Cancer for more than a year. She also hosted a three-part series on difficult conversations that trainees have with their patients. In this episode, we revisit the best of Dr. Yurkiewicz.

'How long do I have left?' 02:59
Anxiety 17:02
Optimism Bias 20:21
Social Support 23:51
Family Dynamics 26:07

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EHA25 highlights: EHA President John Gribben talks AML, myeloma, polycythemia vera, and COVID-19

What were the late-breaking and practice-changing presentations at EHA25 Virtual? John Gribben, MD, DSc, president of the European Hematology Association, highlighted some of them in this podcast.

Dr. Gribben and host David H. Henry, MD, discussed presentations on acute myeloid leukemia (AML), multiple myeloma, polycythemia vera (PV), and COVID-19. Videos of these and other presentations will be available on the EHA25 website until Oct. 15.

Randomized, double-blind, placebo-controlled study of venetoclax with azacitidine vs. azacitidine in treatment-naïve patients with acute myeloid leukemia ineligible for intensive therapy—VIALE-A:

Adding venetoclax to azacitidine improved survival, response, and transfusion independence in older patients with treatment-naïve AML.
Older AML patients have seen “very little progress” in outcomes for decades, but advances such as these are “really moving the field,” Dr. Gribben said.
Abstract LB2601: https://rb.gy/fou9jp
Presentation: https://rb.gy/mmwn6s

Phase 2 randomized trial comparing ropeginterferon versus phlebotomy in low-risk patients with polycythemia vera. Results of the pre-planned interim analysis:

Ropeginterferon was safe and more effective than phlebotomy for keeping hematocrit on target in patients with low-risk PV.
These findings suggest ropeginterferon is a viable option for PV patients, but “old-fashioned phlebotomy can also be quite efficient,” Dr. Gribben said.
Physicians will have to weigh the risks and benefits, including cost-effectiveness, of each treatment, he added.
Abstract LB2602: https://rb.gy/uicnmo
Presentation: https://rb.gy/sj60ia

Isatuximab plus carfilzomib and dexamethasone vs carfilzomib and dexamethasone in relapsed/refractory multiple myeloma (IKEMA): Interim analysis of a phase 3, randomized, open-label study:

Adding isatuximab to carfilzomib-dexamethasone improved progression-free survival and time to next treatment. Overall survival data are not mature.
The study was stopped early because the primary endpoint was met, as isatuximab “clearly demonstrated superiority,” Dr. Gribben noted.
It isn’t clear how isatuximab stacks up against daratumumab, but these results suggest “people now have another CD38 antibody to consider as part of their armamentarium,” Dr. Gribben said.
Abstract LB2603: https://rb.gy/gmxcgk
Presentation: https://rb.gy/v209ol

Endotheliopathy in COVID-19 associated coagulopathy

This study showed “very clear evidence” of endothelial damage contributing to coagulopathy among severely ill patients with COVID-19, Dr. Gribben said.
Endothelial cell and platelet markers were elevated in COVID patients who required intensive care, and soluble thrombomodulin was linked to survival.
These findings prompted the decision to give all COVID patients aspirin.
Abstract LB2605: https://rb.gy/sdc9dv
Presentation: https://rb.gy/nxvpxj

Iron metabolism in health and disease (Plenary I)

This presentation suggested inflammation-induced hypoferremia can predict disease severity in COVID-19 patients.
The presenter posited that iron accumulation in macrophages may increase inflammation and contribute to organ damage in COVID patients.
“You can imagine a whole cascade of events that this virus triggers off,” Dr. Gribben said.
Presentation: https://rb.gy/5lz3d6

Disclosures:

Dr. Gribben reported relationships with Janssen, Celgene, Bristol Myers Squibb, AstraZeneca, AbbVie, Roche, Genentech, and Acerta Pharma.

Dr. Henry reported having no disclosures relevant to this episode.

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The Food and Drug Administration has approved dozens of drugs for new hematology/oncology indications this year. Host David Henry, MD, was joined by David Mintzer, MD, and other colleagues at Penn Medicine in Philadelphia – Justine Cohen, DO, and Ingrid Kohut, DO – to discuss some of these approvals.

Dr. Mintzer reviewed:

The “game-changing” approval of niraparib (Zejula) in advanced ovarian, fallopian tube, or primary peritoneal cancer.
The “exciting” approval of sacituzumab govitecan-hziy (Trodelvy) in metastatic triple-negative breast cancer.
The “COVID-relevant” approval of a new dosing regimen for pembrolizumab (Keytruda) – 400 mg every 6 weeks – across all approved adult indications.
The “niche” approval of mitomycin (Jelmyto) for adults with low-grade upper tract urothelial cancer.
And several other approvals the FDA granted this year.

Details on all approvals are available on the FDA website.

Disclosures:

Dr. Henry and all guests reported having no relevant disclosures.

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What were the practice-changing studies presented at the 2020 ASCO Annual Meeting? Podcast host David H. Henry, MD, and retired oncologist Alan P. Lyss, MD, reviewed 12 studies and assessed their potential impact on treatment.

Breast cancer

Three-year follow-up of neoadjuvant chemotherapy with or without anthracyclines in the presence of dual HER2-blockade for HER2-positive breast cancer (TRAIN-2): A randomized phase III trial. (Abstract 501)

The addition of anthracyclines did not improve event-free or overall survival.
The results suggest patients can avoid the toxicities of anthracycline regimens without compromising efficacy, Dr. Henry said.

KEYNOTE-355: Randomized, double-blind, phase III study of pembrolizumab + chemotherapy versus placebo + chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer. (Abstract 1000)

Pembrolizumab improved responses, particularly in patients with higher PD-L1 expression.
Dr. Lyss noted that pembrolizumab was combined with a “broad range” of chemotherapy regimens in this study.

A randomized phase III trial of systemic therapy plus early local therapy versus systemic therapy alone in women with de novo stage IV breast cancer: A trial of the ECOG-ACRIN Research Group (E2108). (Abstract LBA2)

Early local therapy did not improve disease-free survival or overall survival.
“We probably should not be recommending planned treatment for the intact primary tumor in most women who have stage IV breast cancer,” Dr. Lyss said.

Bladder cancer

Maintenance avelumab + best supportive care (BSC) versus BSC alone after platinum-based first-line (1L) chemotherapy in advanced urothelial carcinoma (UC): JAVELIN Bladder 100 phase III interim analysis. (Abstract LBA1)

Avelumab maintenance prolonged overall survival, although 12% of patients discontinued the treatment due to toxicity.
Because avelumab “meaningfully prolongs overall survival … using it upfront makes a lot of sense,” Dr. Lyss said.

Colorectal cancer

Pembrolizumab versus chemotherapy for microsatellite instability-high/mismatch repair deficient metastatic colorectal cancer: The phase 3 KEYNOTE-177 study. (Abstract LBA4)

Pembrolizumab improved responses and progression-free survival.
All patients with colorectal cancer should be tested for microsatellite instability-high status “because these results really do influence practice immediately,” Dr. Lyss said.
He suggested that pembrolizumab should probably be used as first-line treatment for these patients even though overall survival results are not yet available.

Short-course radiotherapy followed by chemotherapy before TME in locally advanced rectal cancer: The randomized RAPIDO trial. (Abstract 4006)

Short-course radiotherapy followed by consolidative chemotherapy and surgery significantly reduced the rate of treatment failure.
Dr. Lyss called the pathologic complete response rate “impressive” and said it may contribute to a higher rate of rectal preservation.

A randomized phase II/III trial comparing hepatectomy followed by mFOLFOX6 with hepatectomy alone for liver metastasis from colorectal cancer: JCOG0603 study. (Abstract 4005)

There was no improvement in overall survival with mFOLFOX6.
“The take-home to me … is this is probably not a necessary strategy and certainly not standard of care,” Dr. Henry said.

Hodgkin lymphoma

KEYNOTE-204: Randomized, open-label, phase III study of pembrolizumab (pembro) versus brentuximab vedotin (BV) in relapsed or refractory classic Hodgkin lymphoma (R/R cHL). (Abstract 8005)

Pembrolizumab improved progression-free survival.
Dr. Henry marveled that pembrolizumab bested brentuximab vedotin, which previously produced impressive results in patients with relapsed/refractory Hodgkin lymphoma.

Lung cancer

Nivolumab + ipilimumab versus platinum-doublet chemotherapy as first-line treatment for advanced non-small cell lung cancer: Three-year update from CheckMate 227 Part 1. (Abstract 9500)

Nivolumab plus ipilimumab improved overall survival but increased toxicity and treatment discontinuation.
The combination is “not for the faint hearted” but is appropriate for certain patients, Dr. Lyss said, noting there is “room for clinical judgement.”

Osimertinib as adjuvant therapy in patients (pts) with stage IB–IIIA EGFR mutation positive (EGFRm) NSCLC after complete tumor resection: ADAURA. (Abstract LBA5)

Osimertinib improved disease-free survival compared with placebo.
It isn’t clear how osimertinib will impact overall survival, but “we should be using this drug” once it’s approved, Dr. Lyss said.

Smoking cessation (SC) and lung cancer (LC) outcomes: A survival benefit for recent-quitters? A pooled analysis of 34,649 International Lung Cancer Consortium (ILCCO) patients. (Abstract 1512)

Quitting smoking can improve overall survival in lung cancer patients, even if they quit as little as 2 years prior to diagnosis.
“Somewhat counterintuitively, convincing patients to quit smoking at any point in their trajectory, even just prior to their diagnosis, seems to make a difference in survival,” Dr. Lyss said.

Ovarian cancer

Final overall survival (OS) results from SOLO2/ENGOT-ov21: A phase III trial assessing maintenance olaparib in patients (pts) with platinum-sensitive, relapsed ovarian cancer and a BRCA mutation. (Abstract 6002)

Olaparib maintenance improved overall survival and time to next treatment.
Significant benefits were seen in the olaparib arm in spite of a high rate of crossover, Dr. Henry noted.

Disclosures:

Dr. Henry, of Penn Medicine in Philadelphia, reported having no financial disclosures relevant to this episode.

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. He is a columnist for MDedge Hematology/Oncology. He has no other conflicts of interest.

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Jack West, MD, joins the podcast to discuss how he chooses first-line treatment in new patients with non–small cell lung cancer (NSCLC). Dr. West is an associate clinical professor in medical oncology at City of Hope Comprehensive Cancer Center in Duarte, Calif., and a thought leader in thoracic oncology. Dr. West also explores how the COVID-19 pandemic influences treatment approaches, the usefulness of liquid biopsy, and how he weighs the potentially higher risk for COVID-19 complications from checkpoint inhibitors.

Check out Dr. West’s last two appearances on the podcast:

https://www.mdedge.com/podcasts/blood-cancer/immunotherapy-lung-cancer-dr-jack-west-part-1
https://www.mdedge.com/podcasts/blood-cancer/immunotherapy-lung-cancer-dr-jack-west-part-2

Disclosures:

Dr. Henry reported having no financial disclosures relevant to this episode.

Dr. West has a full list of his financial disclosures here.

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David H. Henry, MD, answers the question, "Would you choose oncology again?" This question was asked of oncologists surveyed for the Medscape Oncologist Compensation Report 2020, and 96% of oncologists said they would still choose oncology as their specialty.

Later, William J. Gradishar, MD, of Northwestern University in Chicago, joined Dr. Henry to discuss recent developments in breast cancer. Dr. Gradishar reviewed three trials presented at the 2019 San Antonio Breast Cancer Symposium (SABCS), two of which will be updated at the ASCO Annual Meeting.

SABCS highlights

HER2CLIMB trial:

This trial led to the recent U.S. approval of tucatinib in combination with trastuzumab and capecitabine.
The phase 2 trial enrolled patients with heavily pretreated, HER2-positive, metastatic breast cancer (N Engl J Med. 2020 Feb 13; 382:597-609).
Patients who received tucatinib plus trastuzumab and capecitabine had superior progression-free and overall survival, compared with patients who received placebo plus trastuzumab and capecitabine. Tucatinib even improved outcomes in patients with brain metastasis, Dr. Gradishar noted.
Additional results from HER2CLIMB are scheduled to be presented at ASCO in Abstract 1005.

DESTINY-BREAST01 trial:

This trial led to the U.S. approval of trastuzumab deruxtecan.
Trastuzumab deruxtecan produced durable responses and a median progression-free survival of 16.4 months in patients with HER2-positive, metastatic breast cancer who had previously received trastuzumab emtansine (N Engl J Med 2020; 382:610-621).
A key side effect of trastuzumab deruxtecan is interstitial lung disease, which led to deaths in the trial and a black box warning for the antibody-drug conjugate.
A subgroup analysis of data from DESTINY-BREAST01 is scheduled to be presented at ASCO in Abstract 1036.

KEYNOTE-522 trial:

The phase 3 trial enrolled patients with early triple-negative breast cancer (N Engl J Med 2020; 382:810-821).
The rate of pathologic complete response (pCR) was significantly higher in patients who received pembrolizumab plus neoadjuvant chemotherapy than in patients who received placebo plus neoadjuvant chemotherapy.
Although it is clear that pembrolizumab improves pCR, it isn’t clear if the checkpoint inhibitor will improve long-term outcomes, Dr. Gradishar said.

Disclosures:

Dr. Henry reported having no financial disclosures relevant to this episode.

Dr. Gradishar reported financial relationships with AstraZeneca, Celltrion, Genentech, MacroGenics, Merck, Pfizer, and Seattle Genetics.

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Adam C. Cuker, MD, joins host David H. Henry, MD, to discuss recent findings regarding coagulation in COVID-19 patients. Both Dr. Cuker and Dr. Henry both practice at the Hospital of the University of Pennsylvania in Philadelphia.

Dr. Cuker cited data suggesting at least 25%-30% of patients with COVID-19 develop venous thromboembolism (VTE), despite receiving prophylactic anticoagulation. Furthermore, COVID-19 patients have presented with “lots of different thrombotic manifestations,” he said. This includes stroke and “COVID toes syndrome,” a condition in which patients present with ischemic toes, which appears to have a thromboembolic etiology.

Dr. Cuker suggested that all three aspects of Virchow’s triad may be at play in patients with COVID-19 who have thrombotic manifestations, including:

Circulatory stasis (in patients who are immobilized/sedated/prone/paralyzed).
Hypercoagulability (inflammation, high levels of factor VIII and fibrinogen, neutrophil extracellular traps).
Endothelial injury (SARS-CoV-2 may infect endothelial cells via ACE2).

Dr. Cuker notes that high D-dimer correlates with disease severity and prognosis in COVID-19 patients. He also compares COVID-19 to heparin-induced thrombocytopenia (HIT), noting that both are associated with venous and arterial thromboses. And, like HIT patients, those with COVID-19 may require therapeutic-intensity anticoagulation to prevent clots.

Dr. Cuker says his hospital’s recommendations for anticoagulation in COVID-19 patients are as follows:

Stable hospitalized patients should receive standard-intensity prophylaxis.
ICU patients should receive intermediate- or therapeutic-intensity anticoagulation (at the discretion of the provider).
On discharge, patients should receive low-dose rivaroxaban (Xarelto) at 10 mg daily for 30 days as prophylaxis.
A nonhospitalized patient who has no risk factors for thrombotic events should not receive thromboprophylaxis.

Dr. Cuker also discusses two recent publications on thrombosis and anticoagulation in COVID-19 patients. In one study, thrombotic events occurred in 31% of COVID-19 patients admitted to the ICU at three Dutch hospitals (Thromb Res. 2020 Apr 10. pii: S0049-3848(20)30120-1).

Another study suggested that systemic anticoagulation may improve outcomes of patients hospitalized with COVID-19 (J Am Coll Cardiol. 2020 May 5. pii: S0735-1097(20)35218-9).

Show notes by Emily Bryer, DO, resident in the department of internal medicine, University of Pennsylvania, Philadelphia.

Disclosures:

Dr. Henry has no financial disclosures relevant to this episode.

Dr. Cuker has served as a consultant for Synergy CRO. His institution has received research support on his behalf from Alexion, Bayer, Pfizer, Novo Nordisk, Sanofi, Spark, and Takeda.

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In this episode, Matthew Watto, MD, an internist at Pennsylvania Hospital in Philadelphia, tells host David H. Henry, MD, also of Pennsylvania Hospital, how the COVID-19 pandemic has affected him personally and professionally.

Dr. Watto recounts how COVID-19 has impacted patient volume, shifts, teaching, and interactions between patients and staff. Dr. Watto also discusses his internal medicine podcast, The Curbsiders, which, he says, provides listeners with “clinical pearls, practice-changing knowledge, and bad puns.”

Disclosures:

Dr. Henry has no financial disclosures relevant to this episode. Dr. Watto has no financial disclosures relevant to this episode.

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How should oncologists be treating genitourinary malignancies during the COVID-19 pandemic? Aly-Khan A. Lalani, MD, of McMaster University in Hamilton, Ontario, and colleagues recently published recommendations that help answer that question (Can Urol Assoc J. 2020 May;14[5]:e154-8).

In this episode, Dr. Lalani reviews some of these recommendations with podcast host David H. Henry, MD, of Pennsylvania Hospital in Philadelphia. The pair discuss when and how to use androgen receptor axis-targeted therapies and radium-223 in metastatic prostate cancer, platinum-based chemotherapy in advanced urothelial carcinoma, and checkpoint inhibitors in patients with urothelial carcinoma or renal cell carcinoma.

Disclosures:

Dr. Henry reported having no financial disclosures relevant to this episode.

Dr. Lalani has relationships with Astellas Pharma, Bayer, Bristol-Myers Squibb, Merck, Novartis, Pfizer, Roche/Genentech, TerSera, AbbVie, Eisai, Ipsen, and Janssen.

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The American Society of Clinical Oncology is gearing up for its first-ever virtual meeting at the end of May 2020. ASCO’s president Howard A. “Skip” Burris, III, MD, joins David H. Henry, MD, of Pennsylvania Hospital, Philadelphia, to explain how the virtual meeting will work, from releasing research to earning continuing medical education credits. Dr. Burris also explores how the society is responding to COVID-19.

Later in the podcast, Bernard A. Mason, MD, an oncologist with Pennsylvania Hospital and the University of Pennsylvania, both in Philadelphia, is back with some bonus technology tips for taking notes and syncing them across devices, sharing large files, and best practices for backing up files.

Disclosures:

Dr. Henry reported having no financial disclosures relevant to this episode.

Dr. Burris has a full list of his financial disclosures here.

Dr. Mason reported having no financial disclosures relevant to this episode.

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Oncologists are now weighing the benefits of treating cancer patients against the risk of exposing them to SARS-CoV-2. David Kerr, MD, DSc, of University of Oxford (England) talks with podcast host David H. Henry, MD, of Pennsylvania Hospital in Philadelphia, about how to treat colorectal cancer patients in the COVID-19 era.

Dr. Kerr cowrote an article on MDedge Hematology/Oncology that outlined recommendations for treating colorectal cancer patients during the pandemic. In this episode, Dr. Henry and Dr. Kerr review those recommendations and compare notes on U.K. and U.S. practices.

Disclosures:

Dr. Henry reported having no financial disclosures relevant to this episode. Dr. Kerr has founded three university spin-out companies: COBRA Therapeutics, Celleron Therapeutics, and Oxford Cancer Biomarkers.

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How are community oncologists adapting to the COVID-19 pandemic? Podcast host David H. Henry, MD, of Pennsylvania Hospital in Philadelphia, explores this question with Matthew Lonergan, MD, of Willamette Valley Cancer Institute (WVCI) and Research Center in Eugene, Ore.

Dr. Lonergan explains how WVCI is attempting to minimize staff exposure to COVID-19, how physicians there are dealing with the transition to telemedicine, and how a lack of resources has affected WVCI. Dr. Lonergan and Dr. Henry also discuss how the COVID-19 pandemic has changed research, tumor boards, and other meetings. And the pair compare the response to the current pandemic with the response to HIV and the Spanish flu.

Disclosures:

Dr. Henry reported having no financial disclosures relevant to this episode. Dr. Lonergan reported having no financial disclosures relevant to this episode.

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In the “new normal” of treating cancer patients during COVID-19, when do you decide to start treatment or pause it? Narjust Duma, MD, a thoracic oncologist at the University of Wisconsin, Madison, shares how she makes those decisions in partnership with her lung cancer patients and how the discussions are complicated by the fear and uncertainty around the pandemic.

Later in the podcast, Dr. Duma and podcast host David H. Henry, MD, of Pennsylvania Hospital, Philadelphia, explore how telehealth changes patient encounters, use of liquid biopsies to keep patients out of the hospital, and the importance of checking in with mentees.

Disclosures

Dr. Henry reported having no financial disclosures relevant to this episode. Dr. Duma reported having no financial disclosures relevant to this episode.

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As the nation’s health care system braces for COVID-19 cases, physicians who’ve faced the pandemic first have critical lessons for everyone.

In this bonus episode, two Seattle-area critical care leaders explain how their medical centers are preparing for and responding to their region’s early outbreaks. And they share some creative approaches that are uniting Seattle’s critical care departments.

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Zainab Shahid, MD, medical director of bone marrow transplant infectious diseases at the Levine Cancer Institute/Atrium Health in Charlotte, N.C., breaks down when cancer patients should seek testing for COVID-19 and how they should be treated. Dr. Shahid also compares notes with Blood & Cancer host David H. Henry, MD, of Pennsylvania Hospital in Philadelphia, on how the COVID-19 pandemic has changed the world of medical education.

In Clinical Correlation, Ilana Yurkiewicz, MD, of Stanford (Calif.) University, celebrates National Doctors Day amid the COVID-19 pandemic.

Topics covered in this podcast:

How the education of trainees as changed.
Use of telehealth screening and visits.
COVID-19 case volume and when oncology patients should seek testing.
Which patients should be considered immunocompromised.

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Susan Dent, MD, codirector of the cardio-oncology program at Duke University in Durham, N.C., reflects on virtual grand rounds, telehealth, the screening of patients before clinic visits, and other new realities of cancer care in the age of COVID-19. Dr. Dent also discusses the importance of assessing breast cancer patients for cardiotoxicity.

In Clinical Correlation, Ilana Yurkiewicz, MD, of Stanford (Calif.) University, talks about the importance of advance directives.

Cardiotoxicity in breast cancer treatment

HER2 drugs (such as trastuzumab) and conjugates

If given appropriately, these drugs have limited cardiotoxicity.
The mechanism of cardiotoxicity is a “stunning of the heart.”
If there is a significant drop in left ventricular ejection fraction, hold the drug.
When problems arise, they tend to occur early on.
Important to assess baseline risk factors. Older individuals with underlying hypertension, diabetes, and other conditions need monitoring.

Anthracyclines

The appropriate/safe dose of anthracyclines may be different for each person, based on risk factors such as age and underlying conditions.
Assess patients at baseline using cardiac imaging and biomarkers, and risk factors. If no symptoms of cardiotoxicity, reassess 6-12 months after treatment.
If a patient has poorly controlled hypertension or diabetes, those factors should be better managed to minimize the risk from anthracyclines.

Liposomal anthracyclines

These formulations are less cardiotoxic, but they have not been widely adopted in breast cancer.

Immuno-oncology antibodies

Myocarditis is one of many side effects seen with immunotherapy. It’s not a common side effect (about 1% or less), but when it does occur, it has a 50% fatality rate. Have a high level of suspicion for myocarditis if a patient on immunotherapy presents with shortness of breath and chest pain.

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David Henry, MD, welcomes Bernard A. Mason, MD, to discuss Dr. Mason's favorite digital tools for working as a physician in part 1 of 2.

Dr. Mason is an oncologist with the Pennsylvania Hospital and the University of Pennsylvania, both in Philadelphia.

Dr. Mason explains the actual benefits for doctors and health care providers for popular apps and services from storage to maps. He and Dr. Henry explore the following:

One drive
Google Drive
Google Photos
Google Maps Offline
HERE WeGo

This week's installment of Clinical Correlation, Ilana Yurkiewicz, MD, poses a complicated question about oncologist-patient relationships: Do they ever actually end?

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There’s an art to taking a thorough bleeding history. In this episode, Adam Cuker, MD, director of the Hemophilia and Thrombosis Center at the University of Pennsylvania, Philadelphia, shares the most important questions to ask and the challenges in assessing risk in patients about to undergo surgery and those with active bleeding.

In Clinical Correlation, Ilana Yurkiewicz, MD, of Stanford (Calif.) University, talks about delivering good news to patients.

Practice points:

Always take a thorough bleeding history.
Ask patients about bleeding from head to toe.
Even if the basic laboratory evaluation is normal, the patient may still have a bleeding disorder.

Assessing bleeding risk before surgery

How do you advise patients about to go into surgery who say they bruise easily?

This situation comes up frequently.
In the case of emergency/urgent surgery, there’s not time for a prolonged evaluation.
Take a careful bleeding history: Always ask patients about any history of spontaneous bleeding. Ask about epistaxis, gingival bleeding, rectal bleeding, heavy menstrual periods. Go down the body from head to toe.
It’s also important to ask about hemostatic challenges. Has the patient had any prior surgeries? If it’s a woman, has she had pregnancies and deliveries? Did the patient experience abnormal bleeding with those challenges?
Prompt patients to consider whether they have had surgery that they might not think about, such as tooth extraction, tonsil removal, or polyps removed from their colon.
Seek to establish the time course: Is this a patient who has had abnormal bleeding for their entire life, or did it start later in life? This can provide clues about whether this is a congenital bleeding disorder or an acquired condition.
Ask about such comorbidities as liver and kidney disease, which can be associated with an increased bleeding risk.
Get a complete medication list. Anticoagulants and antiplatelets are the obvious culprits but consider fish oil and selective serotonin reuptake inhibitors (SSRIs) for bleeding.
Ask about family history: Is there a family member who has a diagnosed bleeding disorder or even a history of abnormal bleeding?
Ask about social history: Are you engaged in any activities associated with an increased risk of trauma?
Challenges to taking a bleeding history: Some bleeding symptoms are very common to the normal population. A surprisingly high percentage of people with no bleeding disorders report easy bruising, frequent nose bleeds as a child, heavy menstrual bleeding.

Laboratory work-up

What’s the basic lab evaluation?

Complete blood count (CBC)
Prothrombin time (PT) and partial thromboplastin time (PTT)
Comprehensive metabolic panel to make sure the patient doesn’t have liver or kidney disease

If the basic lab evaluation is normal can they have a bleeding disorder? Yes.

The most common conditions are von Willebrand disease and platelet function disorder.
Less common are rare disorders of fibrinolysis or blood vessel disorders that can lead to abnormal bleeding.

Assessing patients with active bleeding (post catheterization)

Consider whether bleeding is a complication of the procedure or a bleeding disorder.
An efficient but thorough bleeding history is critical.
Order a basic lab work-up and review medications looking for antiplatelet medications in particular.
This approach is a very similar to a patient without active bleeding who is going into surgery.

Direct oral anticoagulants (DOACs) and bleeding

PT and PTT are insensitive to DOACs but order them anyway if the patient is bleeding.
If the test is prolonged, that could suggest that there are substantial levels of drug in circulation.
If the test results come back normal, that doesn’t rule out the possibility that there are clinically meaningful levels of drug circulation that are contributing to bleeding.
Getting a rapid anti-Xa assay could provide more information, but many clinicians don’t have access to that test.
If you can’t get the definitive lab test and the patient is having a serious bleed, err on the side of giving the reversal agent.

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Ever read through a study and wondered how to apply the hazard ratio, or if you should change your practice because of a secondary endpoint finding? In this episode, Lauren M. Catalano, MD, of the University of Pennsylvania, Philadelphia, explains all the common terms and why they matter in the context of the KEYNOTE-024 trial.

In Clinical Correlation, Ilana Yurkiewicz, MD, of Stanford (Calif.) University, talks about how to prepare for an unexpected bad outcome.

Practice points:

Don’t skip over the statistical analysis portion of a paper.
Use Google to find simple definitions for unfamiliar biostatistics terms.
Understanding the statistical elements is essential to determining the quality of the research.

Understanding statistics in the context of KEYNOTE-024

Article discussed: Updated analysis of KEYNOTE-024: Pembrolizumab versus platinum-based chemotherapy for advanced non–small cell lung cancer with PD-L1 tumor proportion score of 50% or greater. J Clin Oncol. 2019 Mar 1;37(7):537-46.

Primary endpoint:

The outcome that is necessary to ensure the efficacy of the trial. What is the study’s objective?
The primary endpoint is defined prior to starting the study, which influences how many patients need to be enrolled to ensure statistical significance.
This paper’s primary endpoint: Time since random assignment to disease progression or death.

Secondary endpoint:

These are interesting trends or observations that the investigators were able to determine, but for which the original study may not have been powered, meaning that they may not have enough data to determine the statistical significance.
This paper’s secondary endpoints: Objective response rate (confirmed complete and partial responses) and safety.

Hazard ratio:

“Ratio” suggests that this is a comparison between the intervention and control arm.
HR is a measure of an effect or intervention on the outcome of interest over a period of time (risk per unit of time). The outcome can be positive or negative.

Confidence interval:

Since it is not possible to survey the entire population, a confidence interval provides a range of values where the true value most likely falls.
If the confidence interval crosses “1” then there is no difference between the arms of the study.

Kaplan-Meier curve:

Often used to illustrate survival.
This is a graphical representation of hazard ratio, usually drawn as a step function.

P value:

The degree of error that we are willing to accept.
Often P = .05, which means we are willing to accept a 5% risk that the hypothesis is incorrect.

Crossover:

Patients assigned in one arm of the study (usually the control arm) can be reassigned to the other arm (usually the intervention group).

Intention to treat:

A technique used in randomized, controlled trials in which patient outcomes are compared within the group the patient was originally assigned to. This may not reflect the treatment that the patient actually received.
If the patient is in a group that is treated but then leaves that group, they are still counted in the original group.

Show notes by Ronak Mistry, DO, resident in the department of internal medicine, University of Pennsylvania, Philadelphia.

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A diagnosis of acute myeloid leukemia (AML) was once an emergency, requiring immediate treatment. Today, the need to start treatment is still urgent, but many patients can benefit by waiting a few days for testing to reveal a fuller picture of the disease. That’s the advice of James M. Foran, MD, of the Mayo Clinic. He joins Blood & Cancer host David H. Henry, MD, of the Pennsylvania Hospital, Philadelphia, to walk through some patient scenarios and the newest treatment options.

In Clinical Correlation, Ilana Yurkiewicz, MD, of Stanford (Calif.) University, talks about what patients do and do not remember from their visits.

Practice points:

Rapid testing results can drive important choices in the initial treatment of AML.
Adjunctive therapies may improve survival by 7%-20% in appropriate patients.

Although a total work-up may take up to 2 weeks, new research suggests it is feasible to get rapid sequencing/cytogenetic testing and assign treatment within 7 days.

Treatment varies:

Daunorubicin and cytarabine (Vyxeos) are still central treatment strategies, but there may be survival advantages (7%-20% improvement) by adding adjunctive therapies, if indicated. A few are listed below:

Liposomal formulations of daunorubicin-cytarabine (CPX351) can have survival advantages in therapy-related AML or AML with myelodysplastic syndrome (MDS)-related changes.
Gemtuzumab (Mylotarg) may be indicated for core binding factor (CBF) AML.
Midostaurin (Rydapt) may improve survival in patients with FMS-like tyrosine kinase (FLT) 3
Enasidenib (Idhifa) may be indicated in patients with IDH mutations.

Options for elderly patients:

In a recent study, CC 486 (oral azacitidine) showed a significant survival advantage and remission duration in elderly patients with AML. The drug is not yet available but could eventually be a maintenance therapy option for patients who do not go on to transplant.

Azacitidine, plus or minus an IDH2 inhibitor, showed much higher remission rates in elderly patients, but did not translate into a survival advantage.

AML in the outpatient setting:

Many patients with AML are being increasingly managed as outpatients, which ultimately will require a different kind of support infrastructure in our hospitals and clinics.

Show notes by Debika Biswal Shinohara, MD, PhD, resident in the department of internal medicine, University of Pennsylvania, Philadelphia.

Dr. Henry and Dr. Yurkiewicz reported having no financial conflicts relevant to this episode. Dr. Foran reported advisory board membership with Pfizer, Jazz Pharma, and Novartis.

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The million-dollar question in the treatment of chronic lymphocytic leukemia (CLL) is what to do after a patient relapses following treatment with venetoclax. Anthony Mato, MD, and Lindsey Roeker, MD, both of Memorial Sloan Kettering in New York, join podcast host David H. Henry, MD, of Pennsylvania Hospital, Philadelphia, to explore the evidence about this question and to review the initial patient work-up and treatment strategies.

In Clinical Correlation, Ilana Yurkiewicz, MD, of Stanford (Calif.) University, discusses patients compliance and how clinician biases can influence compliance.

Practice points:

For patients with CLL with unmutated immunoglobulin variable heavy chain gene (IgVH), novel agents are the first therapy.
Evidence is limited about the best treatment approach after relapse on venetoclax.

Initial work-up in patients with CLL

The initial work-up for patients with CLL is often fluorescent in situ hybridization (FISH), looking for trisomy 12, as well as deletion of 13q, 17p, and 11q.
Next-generation sequencing is used to look for mutations in TP53 and IgVH mutational analysis is done to recognize whether a patient is mutated.
IgVH-mutated patients tend to respond better to therapy.

When to treat

Henry recommends the “if it bothers you, it bothers me” approach, noting that indications for treatment include fever, chills, night sweats, lumps and bumps in the neck, large liver and spleen, and high creatine.

Progression

If a patient is IgVH unmutated, that takes chemoimmunotherapy combinations off the table, regardless of whether the patient is young or fit. Instead, they are on a pathway to receive a novel agent as first therapy.
The choices for novel agents keep expanding. Some standards include ibrutinib plus or minus obinutuzumab, venetoclax plus obinutuzumab, and acalabrutinib plus or minus obinutuzumab.
Each of these combinations has different adverse event profiles and dose schedules. Patient preferences and comorbidities should drive decision making on novel combinations.

Relapse

The million-dollar question: What is the best treatment following relapse on venetoclax?
The answer is unclear but there are generally two choices: Re-treat with the same regimen or switch to a Bruton’s tyrosine kinase (BTK) inhibitor.
There are limited data on re-treatment and emerging data on BTK inhibitors after venetoclax that points to success.

Disclosures

Dr. Anthony Mato reported research funding from DTRM Biopharma and Gilead; consultancy and research funding from Genentech, Pharmacyclics, TG Therapeutics, Adaptive, Sunesis, AstraZeneca, Abbvie, LOXO, and Johnson & Johnson; and consultancy with Verastem, Acerta, Janssen, and Celgene.

Dr. Lindsey Roeker reported minority ownership interest in Abbvie and Abbott Laboratories, ASH grant funding.

Dr. Henry and Dr. Yurkiewicz reported no relevant financial conflicts.

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Chimeric antigen receptor (CAR) T-cell therapy is one of the hottest advances in lymphoma treatment, but who should get it and what does the process look like? Allison Winter, MD, of the Cleveland Clinic helps answer those questions on the podcast. She joins Blood & Cancer host David H. Henry, MD, of the Pennsylvania Hospital, Philadelphia, to break down the side effects and look ahead to possible off-the-shelf products.

In Clinical Correlation, Ilana Yurkiewicz, MD, of Stanford (Calif.) University, discusses optimism bias. She recalls a time when a patient’s drive for optimism affected what she told them and whether that was a good or bad thing.

Practice points:

The time to refer a patient for CAR T-cell therapy is at relapse.
CAR T-cell therapy side effects are serious and include cytokine release syndrome and neurotoxicity.

CAR T-cell therapy use in lymphoma

For patients with diffuse large B-cell lymphoma, treatment after relapse typically involves salvage therapy, and if they are chemotherapy-sensitive, autologous transplant.
The time to refer a patient for CAR T-cell therapy (or other clinical trial options) is at the time of relapse.
CAR T cells are currently approved after two lines of therapy.
What is the process for a patient to get CAR T-cell therapy?
- Evaluation by physicians.
- Approval of insurance.
- Collection of the patient’s T cells.
- Shipment of T cells for genetic modification (takes several weeks).
- Reception of genetically modified T cells by patients.
- Administration of lymphodepleting chemotherapy.
- Admission to the hospital for CAR T-cell infusion.
The median time to get CAR T cells is 26 days.
Allogeneic CAR T-cell products (called off-the-shelf) are in the clinical trial stage.
The two major side effects of immunotherapy include cytokine release syndrome and neurotoxicity.

Reference:

Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017 Dec 28; 377:2531-44.

Show notes by Emily Bryer, DO, resident in the department of internal medicine, University of Pennsylvania, Philadelphia.

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Think of biosimilars as your mother’s minestrone soup: It’s the same recipe and ingredients every time, but not every batch is chemically identical, even if it tastes about the same. That’s how Brian T. Hill, MD, PhD, of the Cleveland Clinic, describes biosimilars. He joins Blood & Cancer host David H. Henry, MD, of Pennsylvania Hospital, Philadelphia, to discuss how biosimilars are made and approved, and how they differ from generic drugs.

In Clinical Correlation, Ilana Yurkiewicz, MD, of Stanford (Calif.) University, talks about percentages -- what they mean, what they don’t mean, and how they can be interpreted in oncology.

What are biosimilars?

Monoclonal antibodies and biologics are complex and large proteins that are made in cells and bioreactors. Because they are made in “nature” instead of a synthetic reaction (discussed with generics), slight differences can be expected in the molecular structure.
Those slight variances do not create clinically meaningful differences between the biosimilar and the original product.
Biosimilars go through very stringent review by the Food and Drug Administration and head-to-head clinical trials with the originator drug.

Biosimilar vs. generic drug

This is in contrast to a “generic” drug. In generic drugs, the chemical composition of all brands is synthesized identically.
An insurance company may approve a biosimilar, but not the originator drug.
Monoclonal biosimilars are on the way as the patent expires; this could soon mean that Herceptin (trastuzumab) will have a biosimilar.

Points:

Insurance driven or otherwise, both Dr. Hill and Dr. Henry would be comfortable using biosimilars.

Show notes by Ronak Mistry, DO, resident in the department of internal medicine, University of Pennsylvania, Philadelphia.

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Blood & Cancer takes you behind the podium at the American Society of Hematology annual meeting for an in-depth look at the latest developments in anemia and myelodysplastic syndrome, chimeric antigen receptor (CAR) T-cell therapy for mantle cell lymphoma, use of novel agents in follicular lymphoma, and a range of new advances being explored in chronic lymphocytic leukemia.

Guests on the podcast include Brian T. Hill, MD, PhD, and Allison Winter, MD, both with the Cleveland Clinic, and Anthony Mato, MD, and Lindsey E. Roeker, MD, of Memorial Sloan Kettering Cancer Center in New York.

Plus, in Clinical Correlation, Ilana Yurkiewicz, MD, of Stanford (Calif.) University, talks about the gratitude that can come from surviving cancer.

ASH19 abstracts discussed in this podcast:

Abstract 843: Roxadustat in the treatment of anemia in patients with lower-risk myelodysplastic syndrome and low red blood cell transfusion burden.

Abstract 754: (03:45) KTE:X19, an anti-CD19 CAR T-cell therapy in patients with relapsed/refractory mantle cell lymphoma: Results of the phase 2 ZUMA-2 trial.

Abstract 3982: (08:28) Comparative outcomes of relapsed follicular lymphoma patients treated with novel agents: A multi-center analysis.

Abstract 31: (13:45) ELEVATE TN: Phase 3 study of acalabrutinib combined with obinutuzumab or alone versus obinutuzumab plus chlorambucil in patients with treatment-naïve chronic lymphocytic leukemia.

Abstract 33: (19:01) Ibrutinib and rituximab provides superior clinical outcome compared to FCR in younger patients with chronic lymphocytic leukemia: Extended follow-up from the E1912 trial.

Abstract 36: Quantitative analysis of minimal residual disease shows high rates of undetectable MRD after fixed-duration chemotherapy-free treatment and serves as surrogate marker for progression-free survival: A prospective analysis of the randomized CLL14 trial.

Abstract 355: Four-year analysis of Murano study confirms sustained benefit of time-limited venetoclax-rituximab in relapsed/refractory chronic lymphocytic leukemia.

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When it comes to treating pain related to sickle cell disease, consider the underlying factors, from constipation to compression spine deformity. That’s just some of the advice from Ifeyinwa Osunkwo, MD, of Atrium Health and Levine Cancer Institute in Charlotte, N.C. She joins host David H. Henry, MD, of Pennsylvania Hospital, Philadelphia, to discuss her tips for treating pain and other complications of sickle cell disease. Dr. Osunkwo also provides an update on progress toward a cure in sickle cell disease that could be available to a large number of patients.

Plus, in Clinical Correlation, Ilana Yurkiewicz, MD, of Stanford (Calif.) University, talks about why treating patients with cancer doesn’t make her sad.

Treating pain in sickle cell:

In sickle cell disease, patients have acute episodes of vaso-occlusive crisis, as well as chronic pain.
Consider whether the pain symptoms are an acute exacerbation of their chronic pain, an independent acute episode of pain, or chronic pain.
In her practice, Dr. Osunkwo has moved to less chronic opioid use and more adjuvant use. She says treat the pain but look for the reason underlying it. The pain could be a result of bone damage, a compression spine deformity, constipation, or other factors related to their disease or the treatment.
Consider the impact of opioid withdrawal after receiving a high dose in the hospital.

Treating acute chest syndrome:

Acute chest syndrome is usually not subtle in its presentation. It is acute and includes fever, pain, difficulty breathing or shortness of breath, hypoxia, and the patient looks sick.
Consider their last chest x-ray and look for changes. Is this a new pulmonary infiltrate?
This is a patient who should be transfused to get them out of distress.
Most of acute chest syndrome cases happen 3 days into a hospital admission.

Developments in sickle cell treatment:

Two new drugs to treat sickle cell symptoms were approved in the United States in 2019: voxelotor (Oxbryta) to increase hemoglobin and crizanlizumab-tmca (Adakveo) to reduce the frequency of vaso-occlusive crisis.
What is coming next? Researchers are working on potential cures for sickle cell that would be available to patients on a widespread basis. That includes haploidentical transplant and gene therapy.

American Society of Hematology guidelines on the treatment of sickle cell complications.

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Daniel G. Haller, MD, of the University of Pennsylvania, Philadelphia, joins Blood & Cancer host David H. Henry, MD, also of the University of Pennsylvania, to review the top three GI cancer trials presented at the 2019 ESMO World Congress on Gastrointestinal Cancer, and how they are changing practice.

Plus, in Clinical Correlation, Ilana Yurkiewicz, MD, of Stanford (Calif.) University, talks about the difficulty in using age to guide cancer treatment.

BEACON trial for colorectal cancer

Patients with BRAF mutations have a poor prognosis and typically fail treatment prior to second line therapy.
BEACON is a phase 3 trial that was designed to test BRAF/MEK combination targeted therapies in patients with BRAF-mutated metastatic colorectal cancer.
The study found that the three-drug combination of encorafenib, binimetinib, and cetuximab significantly improved overall survival in patients with BRAF-mutated metastatic colorectal cancer. The response rate for targeted triple therapy was 26%, compared with 2% for controls.
It may be important for all patients with colorectal cancer to be tested for BRAF.

IDEA trial in colon cancer

Use of oxaliplatin in chemotherapy treatment regimens results in improvement in outcomes for patents with stage III colon cancer. However, treatment with oxaliplatin can cause disabling neuropathy, which is directly proportional to the cumulative dose administered.
The IDEA (International Duration Evaluation of Adjuvant Therapy) trial combines data from six trials, in which patients with stage III colon cancer were randomized to receive 3 months or 6 months of adjuvant chemotherapy with a fluoropyrimidine plus oxaliplatin.
The incidence of peripheral neuropathy was significantly reduced with the 3-month regimen, as compared with 6- month treatment. Survival data for 3 months of treatment with oxaliplatin are still pending.
In patients with positive circulating tumor DNA (ctDNA) prior to adjuvant therapy, 6 months of treatment was preferable.

Pembrolizumab, plus or minus chemotherapy, in gastric cancer

This was a well-balanced three-arm study which included groups of patients treated upfront with pembrolizumab alone, chemotherapy alone, or a combination of pembrolizumab with chemotherapy. The primary endpoint was overall survival.
Pembrolizumab was noninferior to chemotherapy if the combined positive score (CPS) was greater than 1. Pembrolizumab plus chemotherapy was not superior, even for CPS greater than 0.85.
When pembrolizumab is started alone, patients drop off quickly. However, the responders to pembrolizumab have a long duration of response. It may be beneficial to start with chemotherapy and switch to targeted therapy when the side effects of chemotherapy become too great.

Show notes by Debika Biswal Shinohara, MD, PhD, resident in the department of internal medicine, University of Pennsylvania, Philadelphia.

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Thomas LeBlanc, MD, of Duke Cancer Institute in Durham, N.C., joins host David H. Henry, MD, of Pennsylvania Hospital, Philadelphia, to discuss the evolution of the palliative care field and some of the underrecognized ways that it can improve care for hematology-oncology patients.

Plus, in Clinical Correlation, Ilana Yurkiewicz, MD, of Stanford (Calif.) University, shares the story of a patient who put aside her own desire for hospice because of family pressure to pursue curative treatment.

Palliative medicine has evolved tremendously over the past decade; it used to be synonymous with hospice and dying. It is now a sophisticated medical subspecialty with growing and large evidence base.
Palliative treatments are aimed at maximizing patient's quality of life and can be provided alongside other curative treatments.
Physicians, physician assistants, and nurse practitioners form an interdisciplinary team along with patients and their families.
Palliative care specialists can work alongside oncologists to optimize symptom management in patients with multiple or refractory/severe symptoms, including chemotherapy-induced nausea and pain neuropathy.
Palliative care specialists also can help provide a safe space and an extra layer of support to patients having difficulty coping with illness.
The American Society of Clinical Oncology (ASCO) has developed a guideline that all patients with advanced cancer should be receiving dedicated palliative care services concurrent with active treatment.
Workforce shortages in palliative care are limiting access for patients with cancer.

Resource:

Integration of palliative care into standard oncology care: ASCO Practice Guideline update (2017)

Show notes by Debika Biswal Shinohara, MD, PhD, resident in the department of internal medicine, University of Pennsylvania, Philadelphia.

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In this special edition podcast, we bring you the best of Clinical Correlation, a segment on the human side of hematology-oncology care. Clinical Correlation is written, recorded, and produced by Ilana Yurkiewicz, MD, of Stanford (Calif.) University. This episode includes five of our favorite Clinical Correlation segments.

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In this special edition podcast, Blood & Cancer revisits an interview with Ilana Yurkiewicz, MD, of Stanford (Calif.) University. Dr. Yurkewicz is the writer and producer of the podcast’s Clinical Correlation segment, which puts a human face on hematology-oncology care. She sits down with MDedge producer Nick Andrews for a wide-ranging interview that covers everything from the best advice she’s ever gotten to her favorite science fiction writer. The interview first aired on our sister podcast, Postcall.

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Howard “Skip” Burris, MD, chief medical officer of Sarah Cannon Cancer Institute in Nashville, Tenn., joins the podcast to talk about what it’s like to be the 2019-2020 president of the American Society of Clinical Oncology. Dr. Burris joins Blood & Cancer host David H. Henry, MD, of Pennsylvania Hospital, Philadelphia, to share his priorities as president and how he finds the time for advocacy, research, and clinical practice.

Plus, in Clinical Correlation, Ilana Yurkiewicz, MD, of Stanford (Calif.) University, shares the story of a couple who had cancer at the same time.

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David Mintzer, MD, of the University of Pennsylvania, Philadelphia, joins the podcast to discuss noteworthy drug approvals in hematology-oncology in 2019. Dr. Mintzer and Blood & Cancer host, David H. Henry, MD, of Pennsylvania Hospital, Philadelphia, discuss what these new treatment options mean for clinicians and patients.

Plus, in Clinical Correlation, Ilana Yurkiewicz, MD, of Stanford (Calif.) University, is at the annual meeting of the American Society of Hematology with a reminder that the way we talk about patients matters.

Help us make this podcast better! Please take our short listener survey: https://www.surveymonkey.com/r/podcastsurveyOct2019

Dr. Mintzer’s review of new drug approvals in 2019:

https://www.mdedge.com/hematology-oncology/article/211340/mixed-topics/2019-glance-hem-onc-us-drug-approvals?channel=27979

More articles on FDA approvals in hematology-oncology:

https://www.mdedge.com/hematology-oncology/news-fda/cdc

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