Blood Cancer Talks

Dr. Ben Derman, expert in myeloma, discusses key abstracts at ASH23 including new diagnostic criteria for light chain MGUS, trials comparing Dara-VRD vs VRD and Isa-KRD vs KRD in newly diagnosed transplant-eligible myeloma, a phase 1/2 study for Daratumumab-Venetoclax-Dexamethasone in early relapsed t(11;14) myeloma, long-term follow-up data on salvage transplant in myeloma, overall survival results of KarMMa-3 trial, and a trial comparing Dara-KRd vs KRd vs VMP-RD in non-transplant eligible patients. The podcast also covers the revised definition of light chain MGUS, the use of Dara in maintenance therapy, Dara Venetoclaxedex in relapse refractory myeloma, survival results of the Karma 3 trials, and comparing CAR-T therapies.

Dr. Toby Eyre, a consultant haematologist at the University of Oxford in the UK, joins the hosts to review the hottest updates in lymphoma from the ASH 2023 meeting. They discuss topics like the promising results of a novel triplet treatment for mantle cell lymphoma and the challenges of conducting trials in high-risk groups. They also explore the question of stopping therapy without consolidation, the use of a BCL2 inhibitor in lymphoma treatment, and the comparison of different treatments for CLL and Hodgkin lymphoma.

Dr. Michael Dickinson, a medical professional specializing in lymphomas, discusses the potential of bispecific antibodies in the clinical management of lymphoma, including their mechanism of action and side effects. He explores the challenges of treating relapse after CAR T cell therapy and the advantages of using biospecific antibodies in patients who have not responded to CAR T cell therapy. The podcast also delves into the toxicity management of bispecific antibodies and the complexities of funding and outpatient treatments for refractory lymphoma. Finally, it explores the difficulties in eliminating chemotherapy from lymphoma treatments and the challenges in running trials for chemo ineligible patients.

In this episode, we dive into the management of newly diagnosed and relapsed FLT3-positive AML with Dr. Alexander Perl.Here are the shownotes:1. Assessment of minimal residual disease in standard-risk AML https://www.nejm.org/doi/full/10.1056/nejmoa1507471 2. RATIFY study: Midostaurin plus chemotherapy for AML with a FLT3 mutationhttps://www.nejm.org/doi/full/10.1056/nejmoa1614359 3. QuANTUM-First trial: Quizartinib plus chemotherapy in newly diagnosed patients with FLT3-internal-tandem-duplication-positive acute myeloid leukaemia (QuANTUM-First): a randomised, double-blind, placebo-controlled, phase 3 trialhttps://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)00464-6/fulltext 4. Benefit of high-dose daunorubicin in AML induction extends across cytogenetic and molecular groupshttps://ashpublications.org/blood/article/127/12/1551/35035/Benefit-of-high-dose-daunorubicin-in-AML-induction 5. Prospective Randomized Comparison of Idarubicin and High-Dose Daunorubicin in Induction Chemotherapy for Newly Diagnosed Acute Myeloid Leukemiahttps://ascopubs.org/doi/10.1200/JCO.2017.72.8618?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed 6. Phase 3 trial of gilteritinib plus azacitidine vs. azacitidine for newly diagnosed FLT3mut+ AML ineligible for intensive chemotherapyhttps://ashpublications.org/blood/article/140/17/1845/486088/Phase-3-trial-of-gilteritinib-plus-azacitidine-vs 7. ADMIRAL: Gilteritinib or Chemotherapy for Relapsed or Refractory FLT3-Mutated AMLhttps://www.nejm.org/doi/full/10.1056/nejmoa1902688 8. Venetoclax Plus Gilteritinib for FLT3-Mutated Relapsed/Refractory Acute Myeloid Leukemiahttps://ascopubs.org/doi/10.1200/JCO.22.00602?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed 9. Levis MJ, Hamadani M, Logan B, et al: BMT-CTN 1506 (MORPHO): A randomized trial of the FLT3 inhibitor gilteritinib as post-transplant maintenance for FLT3-ITD AML. EHA 2023 Hybrid Congress. Abstract LB2711. Presented June 11, 2023. 10. Sorafenib maintenance in patients with FLT3-ITD acute myeloid leukaemia undergoing allogeneic haematopoietic stem-cell transplantation: an open-label, multicentre, randomised phase 3 trial https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(20)30455-1/fulltext?dgcid=raven_jbs_etoc_email

In this episode, we discuss the art of caring for terminally ill patients with Dr. Azra Raza. We also discuss her book titled "The First Cell", where she recounts numerous poignant stories of her patients with terminal cancer, and teaches us how to find hope amidst despair. Link to the book: https://www.amazon.com/First-Cell-Human-Pursuing-Cancer/dp/1541699521

In this episode, we discuss the biology and management of t(11;14) multiple myeloma and the role of venetoclax with Dr. Rafael Fonseca and Dr. Martin Kaiser. Here are the shownotes:1. Excellent tweetorial thread by Dr. Fonseca highlighting some of the historical studies that identified t(11;14) and its prognostic impact in myeloma: https://x.com/Rfonsi1/status/1206004966294294528?s=20 2. Natural history of t(11;14) myeloma in the era of PIs and IMiDs:https://pubmed.ncbi.nlm.nih.gov/28655925/ 3. BELLINI trial (Ven-Bort-Dex vs Bort-Dex in all-comers):https://pubmed.ncbi.nlm.nih.gov/33129376/ 4. Efficacy of Dara-VCD by cytogenetic subgroups in AL Amyloidosis:https://pubmed.ncbi.nlm.nih.gov/36779691/ 5. CANOVA Trial (Ven-Dex vs Pom-Dex in t[11;14]):https://www.clinical-lymphoma-myeloma-leukemia.com/issue/S2152-2650(23)X0011-1?pageStart=0 6. Phase 1/2 trial on Daratumumab-Venetoclax-Dex in Relapsed/Refractory Myeloma:https://pubmed.ncbi.nlm.nih.gov/34388020/ 7. Phase 1/2 trial on Venetoclax-Carfilzomib-Dex in relapsed/refractory myeloma:https://pubmed.ncbi.nlm.nih.gov/34470049/  

In this episode, we discuss the management of primary CNS lymphoma, secondary CNS lymphoma and CNS prophylaxis with Dr. Kate Cwynarski. Here are the shownotes: 1. ASH 2022 data on PET scan in CNS lymphoma - https://ashpublications.org/blood/article/140/Supplement%201/1334/492207/Is-It-Possible-to-Omit-Bone-Marrow-Biopsy-in?searchresult=1  2. Elizabeth Schorb ASH 2022 (MARTA) 65-80 year olds – https://ashpublications.org/blood/article/140/Supplement%201/1773/493224/High-Dose-Chemotherapy-and-Autologous-Stem-Cell?searchresult=1  3. IESLG 32 study (MATRIX) - https://pubmed.ncbi.nlm.nih.gov/27132696/ and https://pubmed.ncbi.nlm.nih.gov/35562406/  4. R-methotrexate procarbazine (PRIMAIN) - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5383936/  5. RW studies: Andy Evens 500 pts >60 - https://pubmed.ncbi.nlm.nih.gov/36965007/  6. LYSA PRECIS study https://pubmed.ncbi.nlm.nih.gov/35834762/  7. IELSG43 study Lugano (https://onlinelibrary.wiley.com/doi/full/10.1002/hon.3163_15)  and ASH late breaking 2022 (https://ashpublications.org/blood/article/140/Supplement%202/LBA-3/493427/Effects-on-Survival-of-Non-Myeloablative)  8. Secondary CNS lymphoma 134 pts UK PR vs CR autograft - https://pubmed.ncbi.nlm.nih.gov/36300776/  9. “How I Treat secondary CNS involvement by aggressive lymphomas?”-     https://pubmed.ncbi.nlm.nih.gov/37702537/   

The podcast discusses the management of high-risk myeloma, including genetic markers and prognostic factors. It explores the impact of Dell 1P32 and other chromosome 1 nuances on newly diagnosed myeloma. Treatment options and the role of autologous transplant are also discussed. Implementation of gene expression profiling and genetic profiling in managing high-risk myeloma is highlighted. The challenges of using synthetic control arms in clinical trials and the management of high-risk myeloma are explored.

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: 1. “How I Treat Peripheral T-cell Lymphoma?”:https://pubmed.ncbi.nlm.nih.gov/24615779/2. ECHELON-2- RCT of CHOP vs BV-CHP in CD30-positive peripheral T-cell lymphomas:https://pubmed.ncbi.nlm.nih.gov/34921960/3. Ro-CHOP Phase III study (LYSA): Romidepsin-CHOP vs CHOP in peripheral T-cell lymphoma:https://pubmed.ncbi.nlm.nih.gov/34843406/4. 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/33512419/5. A phase 2 biomarker-driven study of ruxolitinib in T-cell lymphomas:https://pubmed.ncbi.nlm.nih.gov/34653242/6. JACKPOT8 study: Selective JAK1 inhibitor in relapsed/refractory peripheral T-cell lymphoma:https://ash.confex.com/ash/2020/webprogram/Paper134650.html

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:1. CCUS and risk of transformation to myeloid neoplasms:https://www.sciencedirect.com/science/article/pii/S0006497121013471 2. Prediction of risk for myeloid neoplasms in clonal hematopoiesis:https://evidence.nejm.org/doi/full/10.1056/EVIDoa2200310 3. CHRS risk score:http://www.chrsapp.com 4. Germline predisposition to clonal hematopoiesis: https://www.sciencedirect.com/science/article/abs/pii/S0145212623006094?via%3Dihubhttps://www.nature.com/articles/s41586-020-2819-2 5. Cancer therapy shapes the fitness landscape of clonal hematopoiesis:https://www.nature.com/articles/s41588-020-00710-0 6. 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 7. Ivosidenib in patients with CCUS and mutations in IDH1:https://classic.clinicaltrials.gov/ct2/show/NCT05030441https://sites.wustl.edu/pimm/