Blood Cancer Talks

In this episode, we discuss with Dr. Martin Kaiser how to identify and manage newly diagnosed high-risk multiple myeloma in the current era of effective frontline therapies. Here are the key studies that we touched upon:

Phase II OPTIMUM (MUKnine) trial in ultra-high-risk myeloma and PCL:

https://pubmed.ncbi.nlm.nih.gov/37315268/

Meta-analysis of >2500 patients with chromosome 1q21 abnormalities:

https://pubmed.ncbi.nlm.nih.gov/34092058/

Predicting ultra-high risk myeloma by molecular profiling (including SKY92 GEP signature):

https://pubmed.ncbi.nlm.nih.gov/32157174/

French data on adverse prognostic impact of del(1p32):

https://pubmed.ncbi.nlm.nih.gov/36375118/

S1211 study: The first high-risk enrichment RCT in myeloma (VRD vs Elo-VRD):

https://pubmed.ncbi.nlm.nih.gov/33357482/

Outcome of “double-hit” patients in MASTER and Dara-VRD arm of GRIFFIN trial:

https://ashpublications.org/blood/article/140/Supplement%201/10144/488521

Impact of Auto-Transplant on decreasing MRD burden in high-risk myeloma (including double-hits):

https://pubmed.ncbi.nlm.nih.gov/35731911/

Preliminary results from GMMG-CONCEPT trial in high-risk myeloma:

https://pubmed.ncbi.nlm.nih.gov/34732857/

View Details

In this episode, we discuss the diagnosis and management of peripheral T-cell lymphoma with Dr. Steven Horwitz, with a focus on the 3 most common types-Peripheral T-cell Lymphoma-NOS, Angioimmunoblastic T-cell Lymphoma (AITL), and Anaplastic Large Cell Lymphoma (ALCL). Here are the key papers we discussed:

“How I Treat Peripheral T-cell Lymphoma?”:
https://pubmed.ncbi.nlm.nih.gov/24615779/
ECHELON-2- RCT of CHOP vs BV-CHP in CD30-positive peripheral T-cell lymphomas:
https://pubmed.ncbi.nlm.nih.gov/34921960/
Ro-CHOP Phase III study (LYSA): Romidepsin-CHOP vs CHOP in peripheral T-cell lymphoma:
https://pubmed.ncbi.nlm.nih.gov/34843406/
RCT of autologous vs allogeneic HSCT as part of 1st line therapy in poor risk peripheral T-cell lymphoma:
https://pubmed.ncbi.nlm.nih.gov/33512419/
A phase 2 biomarker-driven study of ruxolitinib in T-cell lymphomas:
https://pubmed.ncbi.nlm.nih.gov/34653242/
JACKPOT8 study: Selective JAK1 inhibitor in relapsed/refractory peripheral T-cell lymphoma:
https://ash.confex.com/ash/2020/webprogram/Paper134650.html

View Details

In this episode, we discuss the diagnosis and management/monitoring of Clonal Cytopenias of Unknown Significance (CCUS) with Dr. Uma Borate. We also discuss the emerging data on risk stratification and key trials in this space that are currently ongoing. Here are the shownotes:

CCUS and risk of transformation to myeloid neoplasms:
https://www.sciencedirect.com/science/article/pii/S0006497121013471
Prediction of risk for myeloid neoplasms in clonal hematopoiesis:

https://evidence.nejm.org/doi/full/10.1056/EVIDoa2200310

CHRS risk score:

http://www.chrsapp.com

Germline predisposition to clonal hematopoiesis:

https://www.sciencedirect.com/science/article/abs/pii/S0145212623006094?via%3Dihub

https://www.nature.com/articles/s41586-020-2819-2

Cancer therapy shapes the fitness landscape of clonal hematopoiesis:

https://www.nature.com/articles/s41588-020-00710-0

Canakinumab for the prevention of progression to cancer in patients with Clonal Cytopenias of Unknown Significance, IMPACT Study:

https://clinicaltrials.gov/study/NCT05641831?cond=CCUS%20Clonal%20Cytopenia%20of%20Undetermined%20Significance&rank=3

Ivosidenib in patients with CCUS and mutations in IDH1:

https://classic.clinicaltrials.gov/ct2/show/NCT05030441

https://sites.wustl.edu/pimm/

View Details

In this episode, we delve into the diagnosis and management of Paroxysmal Nocturnal Hemoglobinuria (PNH) with Dr. Robert Brodsky.
Here are the shownotes for key papers we discussed in the episode:

How I treat PNH: https://pubmed.ncbi.nlm.nih.gov/33512400/
Alternative donor BMT with posttransplant cyclophosphamide as initial therapy for acquired severe aplastic anemia: https://pubmed.ncbi.nlm.nih.gov/37084383/
Pegcetacoplan versus eculizumab in PNH: a) https://pubmed.ncbi.nlm.nih.gov/33730455/ b) https://pubmed.ncbi.nlm.nih.gov/35349667/
Phase 2 study of danicopan (factor d inhibitor) in patients with paroxysmal nocturnal hemoglobinuria with an inadequate response to eculizumab: https://pubmed.ncbi.nlm.nih.gov/34314483/
Complement and prothrombotic state: https://pubmed.ncbi.nlm.nih.gov/34415298/

View Details

In this episode, we delve into the history of frontline treatment in young/fit patients with Hodgkin's lymphoma and recent developments in the past decade with Dr. Nancy Bartlett from Washington University.

Link for our Blood Cancer Talks Survey: https://bit.ly/BCTS

Here are the key trials we discussed:

RATHL Trial (PET-adapted treatment of Advanced Hodgkin’s Lymphoma):

https://pubmed.ncbi.nlm.nih.gov/27332902/

S0816 (PET-adapted treatment of Advanced Hodgkin’s Lymphoma):

https://pubmed.ncbi.nlm.nih.gov/27069074/

ECHELON-1 (Replacing Bleomycin by Brentuximab Vedotin in Advanced Hodgkin’s Lymphoma):

https://pubmed.ncbi.nlm.nih.gov/29224502/

https://pubmed.ncbi.nlm.nih.gov/35830649/

BREACH (BV-AVD vs ABVD for Early Stage Unfavorable Hodgkin’s Lymphoma):

https://pubmed.ncbi.nlm.nih.gov/35867960/

S1826 (Nivo-AVD vs BV-AVD in Advanced Hodgkin’s Lymphoma):

https://ascopubs.org/doi/abs/10.1200/JCO.2023.41.17_suppl.LBA4

FIL-ROUGE (PET-adapted ABVD vs Dose-Intensified ABVD):

https://onlinelibrary.wiley.com/doi/10.1002/hon.3163_4

HD21 (BRECADD vs EBEACOPP in Advanced Hodgkin’s Lymphoma):

https://onlinelibrary.wiley.com/doi/10.1002/hon.3196_LBA5

View Details

In this episode, we discuss the management of acute toxicities of CAR T-cell therapy, including CRS, ICANS, and HLH with Dr. Michael Jain from Moffitt Cancer Center.

Here are some of the key articles we discussed:

“How I treat refractory CRS and ICANS after CAR T-cell therapy”.

https://pubmed.ncbi.nlm.nih.gov/36989488/

CAR-HEMATOTOX score:

https://pubmed.ncbi.nlm.nih.gov/34166502/

“How I treat cytopenias after CAR T-cell therapy”.

https://pubmed.ncbi.nlm.nih.gov/36800563/

Immune Effector Cell-Associated HLH-Like Syndrome (ASTCT):

https://pubmed.ncbi.nlm.nih.gov/36906275/

ASTCT consensus grading for CRS and ICANS:

https://pubmed.ncbi.nlm.nih.gov/30592986/

Hematopoietic stem cell boost for persistent neutropenia after CAR T-cell therapy:

https://pubmed.ncbi.nlm.nih.gov/35696759/

Modified EASIX score for predicting CRS and neurotoxicity:

https://pubmed.ncbi.nlm.nih.gov/34432870/

View Details

In this episode, we discuss the latest updates on CAR T-cell therapy in multiple myeloma, including the studies presented at ASCO and EHA 2023. Here are the show notes:

For a primer on CAR T-cell therapy, listen to our episode aired on July 22nd 2022 with Dr. Surbhi Sidana: https://share.transistor.fm/s/efc4acf9
RCTs of BCMA CAR T-cell Therapy in Early Relapsed Multiple Myeloma:

a) KarMMa-3 (ide-cel): https://pubmed.ncbi.nlm.nih.gov/36762851/

b) CARTITUDE-4 (cilta-cel): https://pubmed.ncbi.nlm.nih.gov/37272512/

Clinical trials of GPRC5D CAR T-cell therapy in multiple myeloma:

a) MCARH109 (MSKCC Trial): https://pubmed.ncbi.nlm.nih.gov/36170501/

b) POLARIS Trial: https://pubmed.ncbi.nlm.nih.gov/36725117/

Phase 1 UNIVERSAL trial of ALLO-715 in Multiple Myeloma:
https://pubmed.ncbi.nlm.nih.gov/36690811/
Anti BCMA/CD19 CAR T-cells with IMiD maintenance therapy in myeloma:
https://pubmed.ncbi.nlm.nih.gov/36413381/

View Details

In this episode, we delve into the latest data on bispecific antibodies in multiple myeloma with Dr. Ajai Chari. Here are the key studies discussed:

Teclistamab (MajesTEC-1 trial): https://pubmed.ncbi.nlm.nih.gov/35661166/
Correlative analysis from MajesTEC-1 trial: https://ashpublications.org/blood/article/140/Supplement%201/241/487619

3. Talquetamab (MonumenTAL-1 trial): https://pubmed.ncbi.nlm.nih.gov/36507686/

Phase 1 trial of fixed-duration cevostamab:

https://ashpublications.org/blood/article/140/Supplement%201/4415/492339

Phase 1 trial of ABBV-383: https://pubmed.ncbi.nlm.nih.gov/36029527/
Paper summarizing infections with different bispecific antibodies in myeloma: https://pubmed.ncbi.nlm.nih.gov/36716411/

View Details

Excellent overview of Castleman Disease: https://ashpublications.org/blood/article/135/16/1353/452573/Overview-of-Castleman-disease

International consensus guideline for treatment of Idiopathic Multicentric Castleman Disease (iMCD): https://ashpublications.org/blood/article/132/20/2115/39506/International-evidence-based-consensus-treatment

Somatic alterations in Castleman Disease:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9624446/
https://www.nature.com/articles/s41375-018-0323-6

Rituximab + Liposomal Doxorubicin in HHV8-positive MCD:
https://ashpublications.org/blood/article/124/24/3544/33494/Rituximab-plus-liposomal-doxorubicin-in-HIV

RCT on Siltuximab for MCD: https://pubmed.ncbi.nlm.nih.gov/25042199/

Long-term data on Siltuximab in MCD: https://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(19)30257-1/fulltext

View Details

In this episode, we discussed the three CD19-directed chimeric antigen receptor (CAR T-cell) therapies that have been approved for relapsed/refractory aggressive large B cell lymphomas (LBCL) after two lines of therapy:
Axicabtagene ciloleucel (axi-cel) https://www.nejm.org/doi/full/10.1056/nejmoa1707447
Tisagenlecleucel (tisa-cel) https://www.nejm.org/doi/full/10.1056/nejmoa1804980
Lisocabtagene maraleucel (lisocel)https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31366-0/fulltext
Next, we delved into the three prospective phase 3 randomized clinical trials that were conducted to define the optimal second-line treatment by comparing each of the CAR T-cell products to the current standard of care
ZUMA-7 for axicabtagene ciloleucel https://www.nejm.org/doi/full/10.1056/NEJMoa2116133
BELINDA for tisagenlecleucel https://www.nejm.org/doi/full/10.1056/NEJMoa2116596
TRANSFORM for lisocabtagene maraleucel https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)00662-6/fulltext
Then, we briefly discussed the preliminary studies of CAR-T cell therapy in front-line therapy for large B cell lymphoma
Axicabtagene ciloleucel (axi-cel) https://www.nature.com/articles/s41591-022-01731-4

View Details

Key articles and trials discussed in the episode:
1. Excellent review in NEJM on treatment of CLL (2020): https://www.nejm.org/doi/full/10.1056/NEJMra1908213

2. Alliance Trial (Ibrutinib vs chemoimmunotherapy in older patients with untreated CLL): https://www.nejm.org/doi/full/10.1056/NEJMoa1812836

3. E1912 (Ibrutinib vs chemoimmunotherapy in younger/fit patients with CLL): https://www.nejm.org/doi/full/10.1056/NEJMoa1817073

4. RCT testing Acalabrutinib vs Ibrutinib (non-inferiority) in relapsed CLL: https://ascopubs.org/doi/10.1200/JCO.21.01210

5. ELEVATE-TN Study (Acalabrutinib with or without obinutuzumab versus chlorambucil and obinutuzumab): https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30262-2/fulltext

6. CLL-11 trial (showed that obinutuzumab>rituximab in CLL): https://www.nejm.org/doi/full/10.1056/nejmoa1313984

7. Initial data from German CLL-13 trial: https://ashpublications.org/blood/article/138/Supplement%201/71/477548/A-Randomized-Phase-III-Study-of-Venetoclax-Based

8. Ventricular arrhythmia and sudden death with BTK inhibitor: https://ashpublications.org/blood/article-abstract/doi/10.1182/blood.2022016953/486090/Ventricular-Arrhythmias-and-Sudden-Death-Events?redirectedFrom=fulltext\

9. CLL14 trial (venetoclax-obinutuzumab in untreated CLL): https://www.nejm.org/doi/full/10.1056/nejmoa1815281

10. Extended follow-up and MRD dynamics in CLL14 trial: https://ascopubs.org/doi/10.1200/JCO.21.01181

CAPTIVATE Study on fixed-duration Ibrutinib-venetoclax in newly diagnosed CLL: https://ashpublications.org/blood/article/139/22/3278/484114/Fixed-duration-ibrutinib-plus-venetoclax-for-first
Ibrutinib-Venetoclax for treatment of CLL: https://www.nejm.org/doi/full/10.1056/nejmoa1900574
GLOW study (Ibrutinib-Venetoclax vs Chlorambucil-Obinutuzumab): https://evidence.nejm.org/doi/abs/10.1056/EVIDoa2200006

View Details

Key papers discussed in the show:

Pediatric regimen for older adolescents and young adults with ALL: CALGB 10403 https://ashpublications.org/blood/article/133/14/1548/260519/A-pediatric-regimen-for-older-adolescents-and
Dose intensification of daunorubicin and cytarabine during treatment of adult acute lymphoblastic leukemia: C19802 https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.27617
Rituximab in B-ALL https://www.nejm.org/doi/full/10.1056/NEJMoa1605085
A Phase II Trial of Blinatumomab Followed by POMP Maintenance in Older Patients with Newly Diagnosed Philadelphia Chromosome–Negative B-Cell Acute Lymphoblastic Leukemia: SWOG 1318 https://ascopubs.org/doi/abs/10.1200/JCO.21.01766
Blinatumomab for MRD in adults with B-ALL https://ashpublications.org/blood/article/131/14/1522/36655/Blinatumomab-for-minimal-residual-disease-in
Ph-like ALL https://www.nejm.org/doi/10.1056/NEJMoa1403088

View Details

Key papers discussed in the show:
1. Landmark paper on HLA-mismatch and survival: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4568127/

HLA-DP and Risk of GVHD: https://www.nejm.org/doi/full/10.1056/NEJMoa1500140
Outcomes of Allogeneic Transplant with HLA-Mismatched Unrelated Donor: https://ascopubs.org/doi/10.1200/JCO.20.03502
Review/perspective on fundamentals of unrelated donors and cord blood units: https://ashpublications.org/blood/article/120/2/259/30405/A-perspective-on-the-selection-of-unrelated-donors
HLA-DQ heterodimers and HCT: https://ashpublications.org/blood/article-abstract/139/20/3009/484363/HLA-DQ-heterodimers-in-hematopoietic-cell
PT-Cy as GVHD prophylaxis after HCT: https://pubmed.ncbi.nlm.nih.gov/20124511/
Comparative outcome of MUD vs Haplo-HCT from Registry data: https://ashpublications.org/blood/article/138/3/273/475738/HLA-haploidentical-vs-matched-unrelated-donor

View Details

In this episode, we do a thought provoking discussion with Dr. Marty Tallman on mentorship and career development in academic hematology and medical oncology. A must listen for all trainees and early career clinical investigators. Sage wisdom from a legend in the field!

View Details

2021 European LeukemiaNET MRD Working Party Consensus Guidelines: https://pubmed.ncbi.nlm.nih.gov/34724563/

Pre-MEASURE Study ASCO 2022: https://ascopubs.org/doi/abs/10.1200/JCO.2022.40.16_suppl.7006

View Details

https://ascopubs.org/doi/abs/10.1200/JCO.22.00495

View Details

In this episode, we discuss with Dr. Surbhi Sidana the latest advances, practical aspects of patient management, and future directions of cellular therapies in multiple myeloma.

View Details

In this episode, we bring two experts in clonal hematopoiesis, Dr. Sid Jaiswal from Stanford University and Dr. Alex Bick from Vanderbilt University to dissect the biology, potential clinical implications, and future of clonal hematopoiesis.

View Details

BloodCancerTalks is a new podcast focusing exclusively on hematologic malignancies. We will bring a wide range of experts to dig deep into specific topics and critically appraise the literature. Raj Chakraborty is a hematologist/oncologist and an Assistant Professor of Medicine at Columbia University. Ash Kishtagari is a hematologist/oncologist and an Assistant Professor of Medicine at Vanderbilt University.

Blood Cancer Talks: Recent Episodes

Rajshekhar Chakraborty, Ashwin Kishtagari, and Edward Cliff