Blood Cancer Talks

Dr. Andrew Wei, a leading expert in acute myeloid leukemia from the Peter McCallum Cancer Center, discusses the innovative use of venetoclax in treating AML. He highlights groundbreaking clinical trials that have transformed treatment pathways, particularly for older patients. Innovative therapies like venetoclax combined with hypomethylating agents are explored, along with ongoing resistance challenges and the role of genetic mutations in personalized treatment. The conversation also touches on the implications of minimal residual disease negativity in enhancing patient outcomes.

In this episode, we discuss the management of newly diagnosed transplant in-eligible multiple myeloma with Dr. Timothy Schmidt, with a special focus on IMROZ and BENEFIT RCTs testing quadruplets in this space. Here are the key papers we discussed: 1. MAIA trial (Daratumumab-Lenalidomide-Dexamethasone [DRd] vs Rd in newly diagnosed transplant ineligible myeloma): https://pubmed.ncbi.nlm.nih.gov/34655533/2. S0777 trial (VRd vs Rd in newly diagnosed myeloma [transplant-ineligible or transplant-deferred]): https://pubmed.ncbi.nlm.nih.gov/32393732/3. IMROZ trial (Isatuximab-VRd vs VRd in newly diagnosed transplant-ineligible myeloma): https://pubmed.ncbi.nlm.nih.gov/38832972/4. IFM-2020/BENEFIT trial (Isatuximab-VRd vs Isatuximab-Rd in newly diagnosed transplant-ineligible myeloma): https://pubmed.ncbi.nlm.nih.gov/38830994/5. GEM2017FIT trial (VMP-Rd vs KRd vs Dara-KRd in newly diagnosed transplant-ineligible myeloma): https://ashpublications.org/blood/article/142/Supplement%201/209/500199 

In this episode, we discuss updates on low-risk MDS with Dr. Maximilian Stahl with a focus on imetelstat and luspatercept. Here are the trials we discussed: 1. IWG 2019 response criteriahttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7042664/ 2. MEDALIST trial: Luspatercepthttps://www.nejm.org/doi/10.1056/NEJMoa1908892?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed 3. COMMANDS trial : Luspatercept https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)00874-7/abstracthttps://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(24)00203-5/abstract 4. IMerge trial: Imetelstat https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)01724-5/abstract  

In this episode, we discussed the diagnosis and management of polycythemia vera with Dr. Aaron T. Gerds. Here are the shownotes with the key studies discussed: 1.     MIPS PV scoring systemhttps://pubmed.ncbi.nlm.nih.gov/31945802/2.     REVEAL studyhttps://ashpublications.org/blood/article/143/16/1646/506717/Association-between-elevated-white-blood-cell3.     MAJIC PV studyhttps://ascopubs.org/doi/10.1200/JCO.22.01935?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed4.     Cyto-PV Studyhttps://www.nejm.org/doi/full/10.1056/NEJMoa12085005.     PROUD-PV and CONTINUATION-PV trialshttps://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(19)30236-4/abstract6.     RESPONSE clinical trialhttps://www.nejm.org/doi/full/10.1056/NEJMoa14090027.     Rusferitide in PVhttps://www.nejm.org/doi/10.1056/NEJMoa2308809?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed

In this episode, we reviewed the hottest updates in lymphoma from ASCO and EHA 2024, held in Chicago and Madrid respectively, with Dr. Gloria Iacoboni, a haematologist from University Hospital Vall d'Hebron, in Barcelona, Spain. Here are the key abstracts we discussed: 1.      STARGLO: Glofit-GEMOX vs R-GEMOX in relapsed/refractory DLBCLhttps://library.ehaweb.org/eha/2024/eha2024-congress/4136516 2.     Epco-Pola-R-CHP for 1st line DLBCL (EPCORE NHL-5 study):https://library.ehaweb.org/eha/2024/eha2024-congress/422343 3.     3-year follow-up of TRANSFORM (Liso-Cel vs CITàASCT in R/R DLBCL): https://meetings.asco.org/abstracts-presentations/232740 4.     ECHO RCT: Acalabrutinib-BR vs Placebo-BR in previously untreated elderly MCL: https://library.ehaweb.org/eha/2024/eha2024-congress/4136515 5.     HD21: escBEACOPP vs BrECADD in 1st line classical HL: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24)01315-1/fulltext 6.     Combination pirtobrutinib, venetoclax, and obinutuzumab in 1st line CLL: https://library.ehaweb.org/eha/2024/eha2024-congress/422268 7.      Single-agent epcoritamab in Richter’s transformation: EPCORE CLL-1: https://library.ehaweb.org/eha/2024/eha2024-congress/422267

Dr. Benjamin Derman and Dr. Manni Mohyuddin discuss updates in Minimal Residual Disease (MRD) in multiple myeloma, including the potential use of MRD as a surrogate endpoint for accelerated FDA approval. They explore the benefits and challenges of achieving MRD negativity, advancements in MRD detection technologies, implications of MRD resurgence, and the impact of MRD negativity on treatment decisions and discontinuation. The podcast sheds light on the complexities of utilizing MRD in myeloma treatment strategies.

In this episode, we discuss updates in primary myelofibrosis with Dr. Ayalew Tefferi from the Mayo Clinic. The key studies and trials discussed are as follows: ·       GIPSS: Genetically inspired prognostic scoring system that is exclusively based on genetic markers. §  https://www.nature.com/articles/s41375-018-0107-z ·       MIPSS70+ Version 2.0: Mutation and Karyotype-Enhanced International Prognostic Scoring System for Primary Myelofibrosis §  https://ascopubs.org/doi/10.1200/JCO.2018.78.9867?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed ·       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://ashpublications.org/blood/article/142/Supplement%201/620/502738/Transform-1-A-Randomized-Double-Blind-Placebo ·       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://ashpublications.org/blood/article/142/Supplement%201/628/502728/Pelabresib-in-Combination-with-Ruxolitinib-for ·       XPORT-MF-034: Selinexor Plus Ruxolitinib in JAK Inhibitor (JAKi)-Naïve Patients with Myelofibrosis: Long Term Follow up from XPORT-MF-034 Suggestive of Disease Modification 

Experts Dr. Hira Mian and Dr. Manni Mohyuddin discuss maintenance therapy in multiple myeloma, exploring studies like Meta-analysis of CALGB, Myeloma XI RCT, Canadian real-world data, and more. They analyze trials like FORTE and ATLAS, debating options for high-risk patients and emphasizing personalized treatment approaches.

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