S1 Episode 2: Frontline Therapy for Multiple Myeloma

Drs Joseph Mikhael and Shaji Kumar discuss the future of multiple myeloma, including enhanced diagnostics for detecting myeloma, frontline therapy, and durable responses. Relevant disclosures can be found with the episode show notes on Medscape https://www.medscape.com/viewarticle/1002718. The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Multiple Myeloma https://emedicine.medscape.com/article/204369-overview Updated Diagnostic Criteria and Staging System for Multiple Myeloma https://pubmed.ncbi.nlm.nih.gov/27249749/ Mass Spectrometry for the Evaluation of Monoclonal Proteins in Multiple Myeloma and Related Disorders: An International Myeloma Working Group Mass Spectrometry Committee Report https://pubmed.ncbi.nlm.nih.gov/33563895/ Multiple Myeloma Imaging https://emedicine.medscape.com/article/391742-overview Next-Generation Biomarkers in Multiple Myeloma: Understanding the Molecular Basis for Potential Use in Diagnosis and Prognosis https://pubmed.ncbi.nlm.nih.gov/34299097/ Monoclonal Gammopathy of Undetermined Significance https://www.ncbi.nlm.nih.gov/books/NBK507880/ Primary Plasma Cell Leukemia: Consensus Definition by the International Myeloma Working Group According to Peripheral Blood Plasma Cell Percentage https://pubmed.ncbi.nlm.nih.gov/34857730/ Advancing MRD Detection in Multiple Myeloma: Technologies, Applications, and Future Perspectives https://pubmed.ncbi.nlm.nih.gov/40214184/ Genomic Landscape of Multiple Myeloma and Its Precursor Conditions https://pubmed.ncbi.nlm.nih.gov/40399554/ Quadruplet Regimens for Patients With Newly Diagnosed Multiple Myeloma: A Systematic Review and Meta-Analysis https://pubmed.ncbi.nlm.nih.gov/39348665/ Subcutaneous Daratumumab (Dara) + Bortezomib/Lenalidomide/Dexamethasone (VRd) With Dara + Lenalidomide (DR) Maintenance in Transplant-Eligible (TE) Patients With Newly Diagnosed Multiple Myeloma (NDMM): Analysis of Sustained Minimal Residual Disease Negativity in the Phase 3 PERSEUS Trial https://ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.7501 Isatuximab, Carfilzomib, Lenalidomide, and Dexamethasone Induction in Newly Diagnosed Myeloma: Analysis of the MIDAS Trial https://pubmed.ncbi.nlm.nih.gov/39841461/ Comparing Combinations of Drugs to Treat Newly Diagnosed Multiple Myeloma (NDMM) When a Stem Cell Transplant Is Not a Medically Suitable Treatment https://www.clinicaltrials.gov/study/NCT05561387 Cytokine Release Syndrome and Associated Neurotoxicity in Cancer Immunotherapy https://pubmed.ncbi.nlm.nih.gov/34002066/ The Role of CELMoD Agents in Multiple Myeloma https://pmc.ncbi.nlm.nih.gov/articles/PMC12399888/ Phase 2 Study of Talquetamab + Teclistamab in Patients With Relapsed/Refractory Multiple Myeloma and Extramedullary Disease: REDIRECTT-1 https://library.ehaweb.org/eha/2025/eha2025-congress/4173809/shaji.kumar.phase.2.study.of.talquetamab.2B.teclistamab.in.patients.with.html Discovery of a Novel Class NSD2 Inhibitor for Multiple Myeloma With t(4;14) https://pubmed.ncbi.nlm.nih.gov/40949769/ Long-Term (≥5 Year) Remission and Survival After Treatment With Ciltacabtagene Autoleucel (Cilta-Cel) in CARTITUDE-1 Patients (Pts) With Relapsed/Refractory Multiple Myeloma (RRMM) https://ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.7507

Drs Joseph Mikhael and Sigurdur Y. Kristinsson discuss whether it is time to screen for multiple myeloma and what we can learn from the iStopMM study. Relevant disclosures can be found with the episode show notes on Medscape https://www.medscape.com/viewarticle/1002717. The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Multiple Myeloma https://emedicine.medscape.com/article/204369-overview Screening in Multiple Myeloma and Its Precursors: Are We There Yet? https://pubmed.ncbi.nlm.nih.gov/38175579/ Iceland Screens, Treats, or Prevents Multiple Myeloma (iStopMM): A Population-Based Screening Study for Monoclonal Gammopathy of Undetermined Significance and Randomized Controlled Trial of Follow-Up Strategies https://pubmed.ncbi.nlm.nih.gov/34001889/ Identifying Associations Between Race and Gender in the Incidence and Mortality of Patients With Multiple Myeloma https://ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.e20052 Revisiting Wilson and Jungner in the Genomic Age: A Review of Screening Criteria Over the Past 40 Years https://pubmed.ncbi.nlm.nih.gov/18438522/ International Myeloma Foundation https://www.myeloma.org/ Prevalence of Monoclonal Gammopathy of Undetermined Significance https://pubmed.ncbi.nlm.nih.gov/16571879/ Monoclonal Gammopathy of Undetermined Significance https://www.ncbi.nlm.nih.gov/books/NBK507880/ Prevalence and Risk of Progression of Light-Chain Monoclonal Gammopathy of Undetermined Significance: A Retrospective Population-Based Cohort Study https://pubmed.ncbi.nlm.nih.gov/20472173/ Mode of Progression in Smoldering Multiple Myeloma: A Study of 406 Patients https://pubmed.ncbi.nlm.nih.gov/38228628/ Observation or Treatment for Smoldering Multiple Myeloma? A Systematic Review and Meta-Analysis of Randomized Controlled Studies https://pubmed.ncbi.nlm.nih.gov/40419473/

Drs Joseph Mikhael and Peter Voorhees discuss considerations for treating smoldering multiple myeloma, including recent studies and shared decision-making. Relevant disclosures can be found with the episode show notes on Medscape https://www.medscape.com/viewarticle/1002716. The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Observation or Treatment for Smoldering Multiple Myeloma? A Systematic Review and Meta-Analysis of Randomized Controlled Studies https://pubmed.ncbi.nlm.nih.gov/40419473/ Monoclonal Gammopathy of Undetermined Significance https://www.ncbi.nlm.nih.gov/books/NBK507880/ From Criteria to Clinic: How Updated Slim CRAB Criteria Influence Multiple Myeloma Diagnostic Activity https://ascopubs.org/doi/pdf/10.1200/JCO.2024.42.16_suppl.7556 International Myeloma Working Group Risk Stratification Model for Smoldering Multiple Myeloma (SMM) https://pubmed.ncbi.nlm.nih.gov/33067414/ Daratumumab or Active Monitoring for High-Risk Smoldering Multiple Myeloma https://pubmed.ncbi.nlm.nih.gov/39652675/ Lenalidomide-Dexamethasone Versus Observation in High-Risk Smoldering Myeloma After 12 Years of Median Follow-Up Time: A Randomized, Open-Label Study https://pubmed.ncbi.nlm.nih.gov/36067617/ Long-Term Outcome With Lenalidomide and Dexamethasone Therapy for Newly Diagnosed Multiple Myeloma https://pubmed.ncbi.nlm.nih.gov/23648667/ CD38-Directed Therapies for Management of Multiple Myeloma https://pubmed.ncbi.nlm.nih.gov/34235096/ Fixed Duration Therapy With Daratumumab, Carfilzomib, Lenalidomide and Dexamethasone for High Risk Smoldering Multiple Myeloma – Results of the Ascent Trial https://ashpublications.org/blood/article/140/Supplement%201/1830/492739/Fixed-Duration-Therapy-with-Daratumumab Curative Strategy for High-Risk Smoldering Myeloma: Carfilzomib, Lenalidomide, and Dexamethasone (Krd) Followed by Transplant, Krd Consolidation, and Rd Maintenance https://pubmed.ncbi.nlm.nih.gov/39038268/ Early Safety and Efficacy of CAR-T Cell Therapy in Precursor Myeloma: Results of the CAR-PRISM Study Using Ciltacabtagene Autoleucel in High-Risk Smoldering Myeloma https://ashpublications.org/blood/article/144/Supplement%201/1027/531466/Early-Safety-and-Efficacy-of-CAR-T-Cell-Therapy-in

Joseph Mikhael, MD, and Krina K. Patel, MD, MSc, discuss considerations for CAR T-Cell therapy in multiple myeloma, including age, access, and bridging therapy. Relevant disclosures can be found with the episode show notes on Medscape https://www.medscape.com/viewarticle/1002715. The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Multiple Myeloma https://emedicine.medscape.com/article/204369-overview CARTITUDE-1 Final Results: Phase 1b/2 Study of Ciltacabtagene Autoleucel in Heavily Pretreated Patients With Relapsed/Refractory Multiple Myeloma https://ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.8009 Cilta-cel or Standard Care in Lenalidomide-Refractory Multiple Myeloma https://pubmed.ncbi.nlm.nih.gov/37272512/ Plain Language Summary of the KarMMa-3 Study of Ide-cel or Standard of Care Regimens in People With Relapsed or Refractory Multiple Myeloma https://pubmed.ncbi.nlm.nih.gov/38651976/ CAR T-Cell Therapy Toxicity https://www.ncbi.nlm.nih.gov/books/NBK592426/ Immunomodulatory Drugs in Multiple Myeloma: Mechanisms of Action and Clinical Experience https://pubmed.ncbi.nlm.nih.gov/28205024/ Incidence and Outcomes of Cytomegalovirus Reactivation After Chimeric Antigen Receptor T-Cell Therapy https://pubmed.ncbi.nlm.nih.gov/38838226/ Long-Acting Granulocyte Colony-Stimulating Factor in Primary Prophylaxis of Early Infection in Patients With Newly Diagnosed Multiple Myeloma https://pubmed.ncbi.nlm.nih.gov/35064823/ Revisiting the Role of Alkylating Agents in Multiple Myeloma: Up-to-Date Evidence and Future Perspectives https://pubmed.ncbi.nlm.nih.gov/37244325/ Bispecific Antibodies for the Treatment of Relapsed/Refractory Multiple Myeloma: Updates and Future Perspectives https://pubmed.ncbi.nlm.nih.gov/38660139/ FDA Eliminates REMS for Approved CAR T-Cell Therapies https://www.aabb.org/news-resources/news/article/2025/06/30/fda-eliminates-rems-for-approved-car-t-cell-therapies

Drs Joseph Mikhael and Saad Usmani discuss why quadruplet therapy is now the new standard of care for treating newly diagnosed multiple myeloma patients. Relevant disclosures can be found with the episode show notes on Medscape https://www.medscape.com/viewarticle/1002714. The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Daratumumab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma https://pubmed.ncbi.nlm.nih.gov/38084760/ Isatuximab, Lenalidomide, Dexamethasone and Bortezomib in Transplant-Ineligible Multiple Myeloma: The Randomized Phase 3 BENEFIT Trial https://pubmed.ncbi.nlm.nih.gov/38830994/ Daratumumab Plus Bortezomib, Lenalidomide and Dexamethasone for Transplant-Ineligible or Transplant-Deferred Newly Diagnosed Multiple Myeloma: The Randomized Phase 3 CEPHEUS Trial https://pubmed.ncbi.nlm.nih.gov/39910273/ Isatuximab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma https://pubmed.ncbi.nlm.nih.gov/38832972/ A Phase 2 Study of Modified Lenalidomide, Bortezomib and Dexamethasone in Transplant-Ineligible Multiple Myeloma https://pubmed.ncbi.nlm.nih.gov/29740809/ Bortezomib With Lenalidomide and Dexamethasone Versus Lenalidomide and Dexamethasone Alone in Patients With Newly Diagnosed Myeloma Without Intent for Immediate Autologous Stem-Cell Transplant (SWOG S0777): A Randomised, Open-Label, Phase 3 Trial https://pubmed.ncbi.nlm.nih.gov/28017406/ Daratumumab, Lenalidomide, Bortezomib, and Dexamethasone for Transplant-Eligible Newly Diagnosed Multiple Myeloma: The GRIFFIN Trial https://pubmed.ncbi.nlm.nih.gov/32325490/ Carfilzomib Induction, Consolidation, and Maintenance With or Without Autologous Stem-Cell Transplantation in Patients With Newly Diagnosed Multiple Myeloma: Pre-Planned Cytogenetic Subgroup Analysis of the Randomised, Phase 2 FORTE Trial https://pubmed.ncbi.nlm.nih.gov/36528035/ Results of the Phase III Randomized Iskia Trial: Isatuximab-Carfilzomib-Lenalidomide-Dexamethasone Vs Carfilzomib-Lenalidomide-Dexamethasone As Pre-Transplant Induction and Post-Transplant Consolidation in Newly Diagnosed Multiple Myeloma Patients https://www.sciencedirect.com/science/article/abs/pii/S0006497123735416