Medscape InDiscussion: Multiple Myeloma

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

Joseph Mikhael, MD, and Surbhi Sidana, MD, discuss the importance of balancing treatment intervals, managing side effects, and maximizing quality of life in multiple myeloma patients. Relevant disclosures can be found with the episode show notes on Medscape https://www.medscape.com/viewarticle/1002713. The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Acyclovir Prophylaxis Against Varicella Zoster Virus Reactivation in Multiple Myeloma Patients Treated With Bortezomib-Based Therapies: A Retrospective Analysis of 100 Patients https://pubmed.ncbi.nlm.nih.gov/22222250/ Monitoring, Prophylaxis, and Treatment of Infections in Patients With MM Receiving Bispecific Antibody Therapy: Consensus Recommendations From an Expert Panel https://pubmed.ncbi.nlm.nih.gov/37528088/ Characterization of Dysgeusia and Xerostomia in Patients With Multiple Myeloma Treated With the T-Cell Redirecting GPRC5D Bispecific Antibody Talquetamab https://pubmed.ncbi.nlm.nih.gov/38092979/ Idecabtagene Vicleucel for Relapsed/Refractory Multiple Myeloma: Real-World Experience From the Myeloma CAR T Consortium https://pubmed.ncbi.nlm.nih.gov/36623248/ Incidence, Prognostic Impact and Clinical Outcomes of Renal Impairment In Patients With Multiple Myeloma: A Population-Based Registry https://pubmed.ncbi.nlm.nih.gov/31773154/ International Myeloma Working Group https://www.myeloma.org/international-myeloma-working-group IMWG Scientific and Working Committees https://www.myeloma.org/international-myeloma-working-group/imwg-scientific-working-committees

Drs Joseph Mikhael and Brandon Blue reveal the impact of disparities in multiple myeloma and pave a path forward to culturally competent care. Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/964342). The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Multiple Myeloma Awareness and African American Disparities https://www.cancer.gov/about-nci/organization/crchd/blog/2017/multiple-myeloma-disparities Multiple Myeloma https://emedicine.medscape.com/article/204369-overview International Myeloma Foundation https://www.myeloma.org/ International Myeloma Foundation Launches "M-Power Charlotte" to Improve Outcomes in Multiple Myeloma, a Cancer That Disproportionately Affects African Americans https://www.myeloma.org/international-myeloma-foundation-launches-m-power-charlotte-improve-outcomes-multiple-myeloma The Tuskegee Timeline https://www.cdc.gov/tuskegee/timeline.htm

Drs Joseph Mikhael and Nina Shah discuss the exciting future in multiple myeloma in which bispecifics, CELMoDs, modakafusp, and easily delivered CAR T-cell therapy all may play a role. Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/964340). The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources International Myeloma Foundation https://www.myeloma.org/ CAR T-Cell Therapy for Multiple Myeloma https://decisionpoint.medscape.com/oncology/viewarticle/951727 Bispecific Antibodies Versus CAR T-Cells in Multiple Myeloma Treatment: Pros and Cons https://decisionpoint.medscape.com/oncology/viewarticle/967868 Cytokine Release Syndrome https://emedicine.medscape.com/article/2500111-overview Bispecific Antibodies With Multiple Targets Moving Forward in Multiple Myeloma https://ascopost.com/issues/may-10-2022-supplement-hematologic-oncology-almanac/bispecific-antibodies-with-multiple-targets-moving-forward-in-multiple-myeloma/ Study to Evaluate the Safety and Tolerability of CC-92328 in Participants With Relapsed and/or Refractory Multiple Myeloma https://clinicaltrials.gov/ct2/show/NCT04975399 B-Cell Maturation Antigen (BCMA) in Multiple Myeloma: Rationale for Targeting and Current Therapeutic Approaches https://www.nature.com/articles/s41375-020-0734-z GPRC5D Is a Target for the Immunotherapy of Multiple Myeloma With Rationally Designed CAR T Cells https://www.science.org/doi/10.1126/scitranslmed.aau7746 Phase I Study of the Anti-FcRH5 Antibody-Drug Conjugate DFRF4539A in Relapsed or Refractory Multiple Myeloma https://www.nature.com/articles/s41408-019-0178-8 belantamab mafodotin https://reference.medscape.com/drug/blenrep-belantamab-mafodotin-4000056 idecabtagene vicleucel https://reference.medscape.com/drug/abecma-idecabtagene-vicleucel-4000133 ciltacabtagene autoleucel https://reference.medscape.com/drug/carvykti-ciltacabtagene-autoleucel-4000224 A Study of Talquetamab in Participants With Relapsed or Refractory Multiple Myeloma https://clinicaltrials.gov/ct2/show/NCT04634552 Dose-Escalation Study of Cevostamab in Participants With Relapsed or Refractory Multiple Myeloma (R/R MM) https://www.clinicaltrials.gov/ct2/show/NCT03275103 Molecular Mechanisms of Cereblon-Interacting Small Molecules in Multiple Myeloma Therapy https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8623651/ Open-Label Study Comparing Iberdomide, Daratumumab and Dexamethasone (IberDd) Versus Daratumumab, Bortezomib, and Dexamethasone (DVd) in Participants With Relapsed or Refractory Multiple Myeloma (RRMM) (EXCALIBER-RRMM) https://clinicaltrials.gov/ct2/show/NCT04975997 Modakafusp Alfa (TAK-573), an Immunocytokine, Shows Clinical Activity in Patients with Relapsed/Refractory Multiple Myeloma; Updated Results from a First-in-Human Phase 1 Study https://www.sciencedirect.com/science/article/pii/S0006497121028858 A Phase I Study of MCARH109 and MCARH125 CAR T-Cell Therapy in People With Multiple Myeloma https://www.mskcc.org/cancer-care/clinical-trials/22-052

Joseph Mikhael, MD, and Saad Usmani, MD, discuss options in managing triple-class refractory multiple myeloma including selinexor, belantamab mafodotin, and CAR T-cell therapy. Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/964339). 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 Selinexor Prescribing Information https://www.karyopharm.com/wp-content/uploads/2019/07/NDA-212306-SN-0071-Prescribing-Information-01July2019.pdf Belantamab Mafodotin Prescribing Information https://gskpro.com/content/dam/global/hcpportal/en_US/Prescribing_Information/Blenrep/pdf/BLENREP-PI-MG.PDF Cytokine Release Syndrome https://emedicine.medscape.com/article/2500111-overview Trending Clinical Topic: CAR T-cell Therapy https://reference.medscape.com/viewarticle/965011 Consensus Recommendations for the Clinical Management of Patients With Multiple Myeloma Treated With Selinexor https://www.karyopharm.com/wp-content/uploads/2020/06/Consensus-Recommendations_June2020.pdf Selinexor, Bortezomib and Dexamethasone: An Effective Salvage Regimen for Heavily Pretreated Myeloma Patients https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8932935/ Once Weekly Selinexor, Carfilzomib, and Dexamethasone (XKd) in Carfilzomib Nonrefractory Multiple Myeloma (MM) Patients. https://ascopubs.org/doi/abs/10.1200/JCO.2021.39.15_suppl.8038 Ide-cel Prescribing Information https://packageinserts.bms.com/pi/pi_abecma.pdf Belantamab Mafodotin for Relapsed or Refractory Multiple Myeloma (DREAMM-2): A Two-Arm, Randomised, Open-label, Phase 2 Study https://linkinghub.elsevier.com/retrieve/pii/S1470-2045(19)30788-0 DREAMM Trials https://dreammtrials.com/ Blenrep (Belantamab Mafodotin) REMS https://www.accessdata.fda.gov/scripts/cder/rems/index.cfm?event=IndvRemsDetails.page&REMS=403 Band Keratopathy https://emedicine.medscape.com/article/1194813-overview Cilta-cel Prescribing Information https://www.fda.gov/media/156560/download BCMA-Directed CAR T-cell Therapy in Adult Patients With Relapsed and/or Refractory Multiple Myeloma https://clinicaltrials.gov/ct2/show/NCT04318327

Joseph Mikhael, MD, and Ashley Rosko, MD, discuss the role of comorbidities in multiple myeloma and stress the importance of shifting away from the sole use of age-based treatment decisions. Relevant disclosures can be found with the episode show notes on Medscape.com (https://www.medscape.com/viewarticle/964338). 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 International Myeloma Working Group Frailty Score Calculator http://www.myelomafrailtyscorecalculator.net/ R-MCI: Myeloma Comorbidity Index https://www.myelomacomorbidityindex.org/en_calc.html A Simplified Frailty Scale Predicts Outcomes in Transplant-Ineligible Patients With Newly Diagnosed Multiple Myeloma Treated in the FIRST (MM-020) Trial https://www.nature.com/articles/s41375-019-0539-0 Treatment of Multiple Myeloma: ASCO and CCO Joint Clinical Practice Guideline https://ascopubs.org/doi/full/10.1200/JCO.18.02096 Frailty in Older Adults: Evidence for a Phenotype https://academic.oup.com/biomedgerontology/article/56/3/M146/545770 Comprehensive Geriatric Assessment https://www.uptodate.com/contents/comprehensive-geriatric-assessment Carfilzomib or Bortezomib in Combination With Lenalidomide and Dexamethasone for Patients With Newly Diagnosed Multiple Myeloma Without Intention for Immediate Autologous Stem-Cell Transplantation (ENDURANCE): A Multicentre, Open-Label, Phase 3, Randomised, Controlled Trial https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7591827/

Joseph Mikhael, MD, and Peter Voorhees, MD, discuss frontline therapy for multiple myeloma and new options for both transplant-eligible and transplant-ineligible patients. Relevant disclosures can be found with the episode show notes on Medscape.com (https://www.medscape.com/viewarticle/964337). The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources International Myeloma Foundation https://www.myeloma.org/ Lenalidomide, Bortezomib, and Dexamethasone (RVD) Regimen for Multiple Myeloma https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5278911/pdf/i0018-5787-52-1-27.pdf Carfilzomib, Lenalidomide, and Dexamethasone Plus Transplant in Newly Diagnosed Multiple Myeloma https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7714092/ Maintenance With Daratumumab or Observation Following Treatment With Bortezomib, Thalidomide, and Dexamethasone With or Without Daratumumab and Autologous Stem-Cell Transplant in Patients With Newly Diagnosed Multiple Myeloma (CASSIOPEIA): An Open-Label, Randomised, Phase 3 Trial https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(21)00428-9/fulltext Daratumumab, Lenalidomide, Bortezomib, and Dexamethasone for Transplant-Eligible Newly Diagnosed Multiple Myeloma: The GRIFFIN Trial https://ashpublications.org/blood/article/136/8/936/454474/Daratumumab-lenalidomide-bortezomib-and Daratumumab (DARA) Plus Lenalidomide, Bortezomib, and Dexamethasone (RVd) in Patients (Pts) with Transplant-Eligible Newly Diagnosed Multiple Myeloma (NDMM): Updated Analysis of GRIFFIN After 24 Months of Maintenance https://ash.confex.com/ash/2021/webprogram/Paper149024.html Venetoclax or Placebo in Combination With Bortezomib and Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma (BELLINI): A Randomised, Double-Blind, Multicentre, Phase 3 Trial https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(20)30525-8/fulltext Addition of Isatuximab to Lenalidomide, Bortezomib and Dexamethasone As Induction Therapy for Newly-Diagnosed, Transplant-Eligible Multiple Myeloma Patients: The Phase III GMMG-HD7 Trial https://ash.confex.com/ash/2021/webprogram/Paper145097.html Daratumumab, Carfilzomib, Lenalidomide, and Dexamethasone With Minimal Residual Disease Response-Adapted Therapy in Newly Diagnosed Multiple Myeloma https://ascopubs.org/doi/10.1200/JCO.21.01935 Carfilzomib or Bortezomib in Combination With Lenalidomide and Dexamethasone for Patients With Newly Diagnosed Multiple Myeloma Without Intention for Immediate Autologous Stem-Cell Transplantation (ENDURANCE): A Multicentre, Open-Label, Phase 3, Randomised, Controlled Trial https://www.thelancet.com/article/S1470-2045(20)30452-6/fulltext Safety and Effectiveness of Weekly Carfilzomib, Lenalidomide, Dexamethasone, and Daratumumab Combination Therapy for Patients With Newly Diagnosed Multiple Myeloma The MANHATTAN Nonrandomized Clinical Trial https://jamanetwork.com/journals/jamaoncology/fullarticle/2778195 Carfilzomib or Bortezomib in Relapsed or Refractory Multiple Myeloma (ENDEAVOR): An Interim Overall Survival Analysis of an Open-Label, Randomised, Phase 3 Trial https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30578-8/fulltext Carfilzomib With Cyclophosphamide and Dexamethasone or Lenalidomide and Dexamethasone Plus Autologous Transplantation or Carfilzomib Plus Lenalidomide and Dexamethasone, Followed by Maintenance With Carfilzomib Plus Lenalidomide or Lenalidomide Alone for Patients With Newly Diagnosed Multiple Myeloma (FORTE): A Randomised, Open-Label, Phase 2 Trial https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(21)00535-0/fulltext Lenalidomide, Bortezomib, and Dexamethasone With Transplantation for Myeloma https://www.nejm.org/doi/full/10.1056/NEJMoa1611750

Joseph Mikhael, MD, and Irene Ghobrial, MD, discuss screening high-risk populations for early-stage multiple myeloma and new techniques to detect it. Relevant disclosures can be found with the episode show notes on Medscape.com (https://www.medscape.com/viewarticle/964336). The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Long-Term Follow-up of Monoclonal Gammopathy of Undetermined Significance https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5852672/ Prevalence of Monoclonal Gammopathies and Clinical Outcomes in a High-Risk US Population Screened by Mass Spectrometry: A Multicentre Cohort Study https://linkinghub.elsevier.com/retrieve/pii/S2352-3026(22)00069-2 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://www.ncbi.nlm.nih.gov/pmc/articles/PMC8128921/ International Myeloma Working Group Updated Criteria for the Diagnosis of Multiple Myeloma https://linkinghub.elsevier.com/retrieve/pii/S1470-2045(14)70442-5 The IMWG 2/20/20 Risk Stratification Model for Smoldering Multiple Myeloma https://multiplemyelomahub.com/medical-information/the-imwg-22020-risk-stratification-model-for-smoldering-multiple-myeloma