In this episode, we discuss the diagnosis and management of Essential Thrombocythemia with Dr. Raajit Rampal. Here are the shownotes:1.     IPSET (revised) system, risk categories are defined by the presence of a prior thrombosis, age, and JAK2 mutation status:·        Very low risk: No prior thrombosis, age ≤60 years, JAK2-unmutated·        Low risk: No prior thrombosis, age ≤60 years, JAK2-mutated·        Intermediate risk: No thrombosis, age >60 years, JAK2-unmutated·        High risk: History of thrombosis (any age/genotype), or age >60 years with JAK2 mutationhttps://ashpublications.org/blood/article/120/26/5128/30914/Development-and-validation-of-an-International                      2.    The MIPSS-ET provides points for:·        Age > 60 years (3 points)·        Adverse mutation (SF3B1/SRSF2/U2AF1/TP53) (2 points)·        Male sex (1 point)·        White blood cell count ≥11 × 10^9/L (1 point)·        https://onlinelibrary.wiley.com/doi/abs/10.1111/bjh.16380?sid=nlm%3Apubmed 3.    Aspirin o   Is there a benefit of twice-daily aspirin dosing, especially in high-risk or JAK2-mutant disease?https://ashpublications.org/blood/article/136/2/171/454293/A-randomized-double-blind-trial-of-3-aspirin 4.     Cytoreduction in High-risk ET Hydroxyurea: https://www.nejm.org/doi/full/10.1056/NEJM199504273321704 Pegylated interferon alfa MPD-RC 112 Mascarenhas J et al. A randomized phase 3 trial of interferon- α vs hydroxyurea in polycythemia vera and essential thrombocythemia. Blood . 2022) https://ashpublications.org/blood/article/139/19/2931/483404/A-randomized-phase-3-trial-of-interferon-vs Anagrelide in EThttps://ashpublications.org/blood/article/121/10/1720/31186/Anagrelide-compared-with-hydroxyurea-in-WHO 5.    Ruxolitinib  In a randomized study phase 2 study (MAJIC-ET), ruxolitinib treatment did not deliver better rates of hematological response than best-available therapy, although symptoms did improve.  ·        MAJIC-ET study which is a randomized phase 2 trial ·        ET patients resistant/intolerant to HU were randomized to receive RUX or standard treatment (HU 71%, anagrelide 48%, IFN 40%). The primary study outcome was CR, defined by normal platelet and white cell counts and normal spleen size.  ·        At 1 year, response was achieved in 46% of patients in the RUX group and in 44% in the standard arm, without statistically significant difference between the two groups.  ·        In addition, no difference was observed in the rates of thrombosis, hemorrhage, and disease transformation after 2 years of follow-up.  ·        MRs were also uncommon. RUX was superior, however, in symptom control. https://ashpublications.org/blood/article/130/17/1889/36509/Ruxolitinib-vs-best-available-therapy-for-ET

In this episode, we talked about overall survival data from CARTITUDE-4 and KarMMa-3 that was presented at FDA ODAC meeting with Dr. Samer Al Hadidi from University of Arkansas Myeloma Center. 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/FDA ODAC on overall survival data from KarMMa-3 and CARTITUDE-4:https://www.youtube.com/watch?v=VSjdGeeXb40

In this episode, we discuss mentorship and career development as a clinician-investigator with Dr. Ayalew Tefferi from the Mayo Clinic. 

In this episode we discuss the management of newly diagnosed AL amyloidosis with Dr. Angela Dispenzieri from the Mayo Clinic. Here are the key articles discussed:1.      Optimal use of tissue biopsy in AL amyloidosis: https://pubmed.ncbi.nlm.nih.gov/28271734/ 2.     Mayo 2004 staging:  https://pubmed.ncbi.nlm.nih.gov/15365071/ 3.     Mayo 2012 staging: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3675680/ 4.     Renal staging: https://pubmed.ncbi.nlm.nih.gov/25115890/ 5.     Hematologic and cardiac response criteria in AL amyloidosis: https://pubmed.ncbi.nlm.nih.gov/23091105/ 6.     ANDROMEDA Trial: Dara-VCD vs VCD in newly diagnosed AL amyloidosis: https://pubmed.ncbi.nlm.nih.gov/34192431/ 7.      How I Treat AL Amyloidosis: https://pubmed.ncbi.nlm.nih.gov/34517412/ 8.     Venetoclax in AL amyloidosis (largest retrospective study till date): https://pubmed.ncbi.nlm.nih.gov/33431806/

In this episode, we discuss top abstracts in the myeloid space from the American Society of Hematology 2023 meeting with Dr. Anand Patel. Here are the abstracts that were discussed:1. TRANSFORM-1: A Randomized, Double-Blind, Placebo-Controlled, Multicenter, International Phase 3 Study of Navitoclax in Combination with Ruxolitinib Versus Ruxolitinib Plus Placebo in Patients with Untreated Myelofibrosis https://ash.confex.com/ash/2023/webprogram/Paper173509.html 2. MANIFEST-2: Pelabresib in Combination with Ruxolitinib for Janus Kinase Inhibitor Treatment-Naïve Patients with Myelofibrosis: Results of the MANIFEST-2 Randomized, Double-Blind, Phase 3 Study https://ash.confex.com/ash/2023/webprogram/Paper179141.html 3. Venetoclax + Decitabine vs 7+3 in AML https://ashpublications.org/blood/article/142/Supplement%201/970/503790/Comparing-the-Efficacy-and-Safety-of-Venetoclax 4. FILO study: Acute Myeloid Leukemia Patients Who Stopped Venetoclax or/and Azacytidine for Other Reasons Than Progression Have a Prolonged Treatment Free Remission and Overall Survival. https://ash.confex.com/ash/2023/webprogram/Paper185437.html  5. AUGMENT-101: Revumenib Monotherapy in Patients with Relapsed/Refractory KMT2Ar Acute Leukemia: Topline Efficacy and Safety Results https://ash.confex.com/ash/2023/webprogram/Paper172422.html 6. VEN+HMA in HR MDS: Safety, Efficacy, and Patient-Reported Outcomes of Venetoclax in Combination with Azacitidine for the Treatment of Patients with Higher-Risk Myelodysplastic Syndrome: A Phase 1b Study https://ash.confex.com/ash/2020/webprogram/Paper139492.html

In this episode, we talk about GVHD prophylaxis, including recent data on post-transplant cyclophosphamide and abatacept with Dr. Shernan Holtan from the University of Minnesota. Here are the key trials we discussed:1. BMT CTN 1203 trial: Three prophylaxis regimens (tacrolimus, mycophenolate mofetil, and cyclophosphamide; tacrolimus, methotrexate, and bortezomib; or tacrolimus, methotrexate, and maraviroc) versus tacrolimus and methotrexate for prevention of GVHD in allogeneic transplantation. https://pubmed.ncbi.nlm.nih.gov/30824040/ 2. BMT CTN 1703 study: Post-Transplantation Cyclophosphamide-Based GVHD prophylaxis  https://pubmed.ncbi.nlm.nih.gov/37342922/ 3. Patient-Reported Outcomes of BMT CTN 1703 https://ash.confex.com/ash/2023/webprogram/Paper187859.html 4. Phase II Study of Myeloablative 7-8/8-Matched Allotransplantation with Post-Transplantation Cyclophosphamide, Tacrolimus, and Mycophenolate Mofetil https://pubmed.ncbi.nlm.nih.gov/37311510/ 5. BMT CTN 1301 trial: Randomized Phase III BMT CTN Trial of Calcineurin Inhibitor-Free Chronic Graft-Versus-Host Disease Interventions in Myeloablative Hematopoietic Cell Transplantation for Hematologic Malignancies https://pubmed.ncbi.nlm.nih.gov/34855460/ 6. Phase II Trial of Costimulation Blockade With Abatacept for Prevention of Acute GVHD (ABA2) https://pubmed.ncbi.nlm.nih.gov/33449816/ 7. Aurora Kinase a Inhibition for Gvhd and Relapse Prevention after Allogeneic HCT: Phase I Trial in Combination with Ptcy/Sirolimus https://ash.confex.com/ash/2023/webprogram/Paper181292.html

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