Consensus or Controversy? Documenting and Discussing Investigators’ Approaches to the Management of Relapsed/Refractory Multiple Myeloma — Symposium Proceedings

Faculty

TARGET AUDIENCE
This activity is intended for medical oncologists, hematologists, hematology-oncology fellows and other healthcare providers involved in the treatment of multiple myeloma.

LEARNING OBJECTIVES

• Consider published research findings and other clinical factors in the best-practice sequencing of established and novel agents and regimens for patients with relapsed/refractory (R/R) MM.
• Evaluate published research findings to identify patients with R/R MM for whom treatment with chimeric antigen receptor T-cell therapy directed at B-cell maturation antigen (BCMA) should be considered and/or recommended.
• Assess available research data with BCMA- and non-BCMA-directed bispecific antibodies for MM in order to appropriately integrate these agents into clinical algorithms.
• Recall published clinical research establishing the definitive efficacy of BCMA-directed antibody-drug conjugate therapy for patients with R/R MM.
• Analyze the mechanism of action of, efficacy and safety findings with and ongoing research evaluating cereblon E3 ligase modulators to prepare for the potential clinical availability of these agents for patients with R/R MM.
• Implement a plan of care to recognize and manage class-effect and agent-specific toxicities associated with therapies commonly used in the care of patients with R/R MM.
• Recall available data with novel agents and strategies currently under investigation for R/R MM, and as applicable, discuss clinical trial participation with eligible patients.

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CREDIT DESIGNATION STATEMENT
Research To Practice designates this enduring material for a maximum of 2.25 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

AMERICAN BOARD OF INTERNAL MEDICINE (ABIM) — MAINTENANCE OF CERTIFICATION (MOC)
Successful completion of this CME activity, which includes participation in the evaluation component and a post-test, enables the participant to earn up to 2.25 Medical Knowledge MOC points in the American Board of Internal Medicine’s (ABIM) Maintenance of Certification (MOC) program. Participants will earn MOC points equivalent to the amount of CME credits claimed for the activity. It is the CME activity provider’s responsibility to submit participant completion information to ACCME for the purpose of granting ABIM MOC credit.

Please note, this program has been specifically designed for the following ABIM specialties: medical oncology and hematology.

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HOW TO USE THIS CME ACTIVITY
To receive credit for this activity, the participant should review the CME information, watch the video, complete the post-test with a score of 80% or better, and fill out the evaluation.

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Research To Practice (RTP) is committed to providing its participants with high-quality, unbiased and state-of-the-art education and adheres to the ACCME’s Standards for Integrity and Independence in Accredited Continuing Education. Any individuals in a position to control the content of an accredited continuing education activity, including faculty, planners, reviewers and others, are required to disclose all relevant financial relationships with ineligible entities (commercial interests). All relevant financial relationships have been mitigated prior to the commencement of this activity. In addition, all activity content is reviewed by RTP scientific staff and an external, independent physician reviewer for fair balance, scientific objectivity of studies referenced and patient care recommendations.

FACULTY — The following faculty reported relevant financial relationships with ineligible entities:

Dr Alsina — Advisory Committees: Bristol Myers Squibb, Janssen Biotech Inc, Kite, A Gilead Company, Sanofi; Contracted Research: AstraZeneca Pharmaceuticals LP, Bristol Myers Squibb, Janssen Biotech Inc, Pfizer Inc; Data and Safety Monitoring Boards/Committees: Bristol Myers Squibb. Dr Lee — Consulting Agreements (Paid to Institution): AbbVie Inc, Alexion Pharmaceuticals, Allogene Therapeutics, AstraZeneca Pharmaceuticals LP, Bristol Myers Squibb, GSK, Janssen Biotech Inc, Legend Biotech, Medline, Pfizer Inc, Predicta Biosciences, Regeneron Pharmaceuticals Inc, Sanofi, Takeda Pharmaceuticals USA Inc; Consulting Agreements (Paid to Self): Alexion Pharmaceuticals,Allogene Therapeutics, Bristol Myers Squibb, GSK, Janssen Biotech Inc, Menarini Group, Pfizer Inc, Regeneron Pharmaceuticals Inc, Sanofi, Takeda Pharmaceuticals USA Inc; Contracted Research: AbbVie Inc, Alexion Pharmaceuticals, Amgen Inc, AstraZeneca Pharmaceuticals LP, Bristol Myers Squibb, GSK, Janssen Biotech Inc, Menarini Group, Moderna, Regeneron Pharmaceuticals Inc, Takeda Pharmaceuticals USA Inc; Data and Safety Monitoring Boards/Committees: Allogene Therapeutics, Takeda Pharmaceuticals USA Inc. Dr Richardson — Consulting Agreements: Bristol Myers Squibb, Celgene Corporation, GSK, Karyopharm Therapeutics, Oncopeptides, Regeneron Pharmaceuticals Inc, Sanofi; Contracted Research: Oncopeptides.

CONTRIBUTING CLINICAL INVESTIGATORS
Rafael Fonseca, MD — Board of Directors: Antengene; Consulting Agreements: AbbVie Inc, Adaptive Biotechnologies Corporation, Amgen Inc, Apple, Bristol Myers Squibb, Celgene Corporation, GSK, Janssen Biotech Inc, Karyopharm Therapeutics, Pfizer Inc, RA Capital Management, Regeneron Pharmaceuticals Inc, Sanofi; Data and Safety Monitoring Boards/Committees: Bristol Myers Squibb; Patents (Through Institution): Abbott; Scientific Advisory Boards: Caris Life Sciences; Stock Options/Stock — Public Companies: Antengene, Caris Life Sciences. Joseph Mikhael, MD, MEd — Consulting Agreements: Bristol Myers Squibb, Janssen Biotech Inc, Menarini Group, Sanofi.

MODERATOR
Dr Lonial — Advisory Committees and Consulting Agreements: AbbVie Inc, Amgen Inc, Bristol Myers Squibb, Genentech, a member of the Roche Group, GSK, Janssen Biotech Inc, Novartis, Pfizer Inc, Regeneron Pharmaceuticals Inc, Takeda Pharmaceuticals USA Inc; Boards of Directors: TG Therapeutics Inc; Contracted Research: Bristol Myers Squibb,Janssen Biotech Inc, Novartis, Takeda Pharmaceuticals USA Inc; Stock Options/Stock — Public Companies: TG Therapeutics Inc.

RESEARCH TO PRACTICE CME PLANNING COMMITTEE MEMBERS, STAFF AND REVIEWERS — Planners, scientific staff and independent reviewers for Research To Practice have no relevant financial relationships to disclose.

This educational activity contains discussion of published and/or investigational uses of agents that are not indicated by the Food and Drug Administration. Research To Practice does not recommend the use of any agent outside of the labeled indications. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications and warnings. The opinions expressed are those of the presenters and are not to be construed as those of the publisher or grantors.

This activity is supported by educational grants from Bristol Myers Squibb, Genentech, a member of the Roche Group, and GSK.

Release date: July 2026
Expiration date: July 2027

After completing the post-test, learners may download and review the answers here in order to identify further areas of study.

Dr Lee

Chari A et al. Talquetamab, a G protein-coupled receptor family C group 5 member D x CD3 bispecific antibody, in patients with relapsed/refractory multiple myeloma (RRMM): Phase 1/2 results from MonumenTAL-1. ASH 2022;Abstract 384.

Chari A et al. Oral selinexor-dexamethasone for triple-class refractory multiple myeloma. N Engl J Med 2019;381(8):727-38. Abstract

Cirstea D et al. Bispecific outpatient step-up dosing with prophylactic dexamethasone: The BOSS program experience in myeloma. IMS 2025;Abstract PA-017.

Kowalski A et al. Tocilizumab prophylaxis for patients with multiple myeloma treated with bispecific antibodies. Blood Adv 2025;9(19):4979-86. Abstract

Kowalski A et al. Tocilizumab prophylaxis for patients with relapsed or refractory multiple myeloma treated with teclistamab, elranatamab or talquetamab. ASH 2024,Abstract 932.

Li J et al. Membrane-proximal epitope facilitates efficient T cell synapse formation by anti-FcRH5/CD3 and is a requirement for myeloma cell killing. Cancer Cell 2017;31(3):383-95. Abstract

Mateos MV et al. Phase 3 randomized study of teclistamab plus daratumumab versus investigator’s choice of daratumumab and dexamethasone with either pomalidomide or bortezomib (DPd/DVd) in patients (pts) with relapsed refractory multiple myeloma (RRMM): Results of majestec-3. ASH 2025;Abstract LBA-6.

Mian HS et al. Cevostamab plus pomalidomide (pom) and dexamethasone (dex) in relapsed/refractory multiple myeloma (RRMM): Phase I dose-expansion results from the CAMMA 1 study. IMS 2025;Abstract OA-14.

Mina R et al. MajesTEC-9: A phase 3 randomized study of teclistamab monotherapy vs investigator’s choice of pomalidomide, bortezomib, and dexamethasone or carfilzomib and dexamethasone (PVd/Kd) in patients (pts) with relapsed refractory multiple myeloma (RRMM). ASCO 2026;Abstract 7507.

Rasche L et al. Efficacy and safety from the phase 1/2 MonumenTAL-1 study of talquetamab, a GPRC5D×CD3 bispecific antibody, in patients with relapsed/refractory multiple myeloma: Analyses at an extended median follow-up. ASCO 2025;Abstract 7528.

Voorhees P et al. Phase 3, randomized study of talquetamab (tal) plus daratumumab (dara) ± pomalidomide (pom) vs dara plus pom and dexamethasone (DPd) IN relapsed/refractory multiple myeloma (RRMM): MonumenTAL-3. EHA 2026;Abstract S100.

Waldschmidt JM et al. Comprehensive review of bispecific antibody constructs in multiple myeloma: Affinities, dosing strategies and future perspectives. Clin Lymphoma Myeloma Leuk 2025;25(5):309-15. Abstract

Dr Lonial

Dimopoulos MA et al. Updated results from phase 3 DREAMM-8 study of belantamab mafodotin plus pomalidomide and dexamethasone vs pomalidomide plus bortezomib and dexamethasone in relapsed/refractory multiple myeloma. EHA 2025;Abstract PF728.

Dimopoulos MA et al. Belantamab mafodotin, pomalidomide, and dexamethasone in multiple myeloma. N Engl J Med 2024;391(5):408-21. Abstract

Hájek R et al. Characterization of ophthalmic examination findings (OEFs) and impact on reading and driving in patients with relapsed/refractory multiple myeloma (RRMM) treated with belantamab mafodotin (belamaf). EHA 2025;Abstract PS1761.

Hungria V et al. Belantamab mafodotin plus bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma (DREAMM-7): Updated overall survival analysis from a global, randomised, open-label, phase 3 trial. Lancet Oncol 2025;26(8):1067-80. Abstract

Lonial S et al. Belantamab mafodotin (belamaf) ocular events are manageable and reversible with dose modifications guided by standard assessments. ASH 2025;Abstract 4055.

Lonial S et al. Longer term outcomes with single‐agent belantamab mafodotin in patients with relapsed or refractory multiple myeloma: 13‐month follow‐up from the pivotal DREAMM‐2 study. Cancer 2021;127(22):4198-212. Abstract

Lonial S et al. Recovery of ocular events with longer-term follow-up in the DREAMMM-2 study of single-agent belantamab mafodotin (belamaf) in patients with relapsed or refractory multiple myeloma (RRMM). ASH 2020;Abstract 3224.

Mateos MV et al. Patients with relapsed/refractory multiple myeloma who achieved sustained minimal residual disease negativity in the dreamm-7 trial. ASH 2025;Abstract 2265.

Mateos MV et al. Modification of belantamab mafodotin dosing to balance efficacy and tolerability in the DREAMM-7 and DREAMM-8 trials. Blood Adv. 2025;9(22):5708-19. Abstract

Terpos E et al. Practical guidance on clinical management of belantamab mafodotin-associated ocular events. Am J Hematol 2025;100(10):1839-50. Abstract

Trudel S et al. Deep responses and durable outcomes in patients treated with belantamab mafodotin plus pomalidomide and dexamethasone from long-term follow-up of the phase 3 dreamm-8 study. ASH 2025;Abstract 2264.

Trudel S et al. DREAMM-8 study of belantamab mafodotin plus pomalidomide and dexamethasone (BPd) vs pomalidomide plus bortezomib and dexamethasone (PVd) in relapsed/refractory multiple myeloma (RRMM): A subgroup analysis in patients with high-risk cytogenetic features. ASCO 2025;Abstract 7533.

Usmani SZ et al. Optimizing belantamab mafodotin doses for the treatment of transplant-ineligible newly diagnosed multiple myeloma in the DREAMM-9 study. IMS 2025;Abstract PA-416.

Dr Richardson

Amatangelo M et al. Pharmacodynamic changes in tumor and immune cells drive iberdomide’s clinical mechanisms of activity in relapsed and refractory multiple myeloma. Cell Rep Med 2024;5(6):101571. Abstract

Chen LY et al. Mezigdomide treatment in relapsed-refractory myeloma patients shifts bone marrow NK and T cell populations from exhaustion to activation. ASH 2023;Abstract 4686.

Costa LJ et al. Mezigdomide (MEZI) in novel-novel combinations for relapsed or refractory multiple myeloma (RRMM): Preliminary results from the CA057-003 trial. ASH 2024;Abstract 677.

Gay F et al. Iberdomide maintenance after autologous stem-cell transplantation in patients with newly diagnosed multiple myeloma: An update from the phase 2 EMN26 trial. EHA 2024;Abstract P958.

González-Calle V et al. Efficacy and safety of iberdomide, daratumumab, and dexamethasone, in transplant-ineligible newly diagnosed multiple myeloma patients: Initial analysis of the GEM-IBERDARAX trial. IMS 2025;Abstract OA-63.

Jeyaraju D et al. Longitudinal analysis of MRD negativity and immune dynamics in patients with transplant-ineligible newly diagnosed multiple myeloma treated with iberdomide, daratumumab, and dexamethasone from the CC-220-MM-001 trial. ASH 2025;Abstract 2255.

Kegyes D et al. Targeting degradation of IKZF1 and IKZF3 through modulation of the E3 ligase substrates in the context of cellular therapies for multiple myeloma. Biomark Res 2025;13(1):105. Abstract

Landgren O et al. A phase 2 trial of iberdomide, carfilzomib, daratumumab and dexamethasone quadruplet therapy for relapsed/refractory multiple myeloma: The rekindle study. ASH 2025;Abstract 251.

Lim SL et al. An immune-therapeutic salvage strategy for ‘functional’ high-risk (FHR) multiple myeloma (MM) incorporating iberdomide, isatuximab, and dexamethasone — The IBIS study amarc 20-01. ASH 2025;Abstract 5841.

Lonial S et al. EXCALIBER-RRMM: A phase III trial of iberdomide, daratumumab, and dexamethasone in relapsed/refractory multiple myeloma. Future Oncol 2025;21(14):1761-9. Abstract

Lonial S et al. Iberdomide plus dexamethasone in heavily pretreated late-line relapsed or refractory multiple myeloma (CC-220-MM-001): A multicentre, multicohort, open-label, phase 1/2 trial. Lancet Haematol 2022 Nov;9(11):e822-32. Abstract

Mo C et al. Selinexor, mezigdomide, and dexamethasone in patients with relapsed/refractory multiple myeloma who relapsed or are ineligible for T-cell–redirecting therapy: STOMP phase 1 preliminary results. European Myeloma Network Meeting 2026;Abstract P43.

Mo C et al. Mezigdomide for multiple myeloma: A focus on phase 2 trial data. Expert Opin Emerg Drugs 2025;30(3):209-19. Abstract

Mo C et al. Selinexor, mezigdomide, and dexamethasone in patients with relapsed/refractory multiple myeloma who relapsed or are ineligible for T-cell–redirecting therapy: Stomp phase 1 results. ASH 2025;Abstract 4010.

Oriol A et al. Mezigdomide (MEZI) plus dexamethasone (DEX) and bortezomib (BORT) or carfilzomib (CFZ) in patients (pts) with relapsed/refractory multiple myeloma (RRMM): Results from the CC-92480-MM-002 trial. IMS 2023;Abstract OA-49.

Perrot A et al. Isatuximab, carfilzomib, lenalidomide, and dexamethasone induction in newly diagnosed myeloma: Analysis of the MIDAS trial. Blood 2025;146(1):52-61. Abstract

Perrot A et al. Measurable residual disease-guided therapy in newly diagnosed myeloma. N Engl J Med 2025;393(5):425-37. Abstract

Puig N et al. Iberdomide and dexamethasone in elderly patients with newly diagnosed multiple myeloma. EHA 2025;Abstract PS1784.

Richardson PG et al. Safety results from the phase 3 MajesTEC-7 study in patients (pts) with transplant ineligible/not intended newly diagnosed multiple myeloma (NDMM). ASCO 2026;Abstract LBA7506.

Richardson PG et al. A phase 3, two-stage, randomized study of mezigdomide, carfilzomib, and dexamethasone (MeziKd) versus carfilzomib and dexamethasone (Kd) in relapsed/refractory multiple myeloma (RRMM): SUCCESSOR-2. ASCO 2023;Abstract TPS8070.

Richardson PG et al. Mezigdomide (MEZI) plus dexamethasone (DEX) and daratumumab (DARA) or elotuzumab (ELO) in patients (pts) with relapsed/refractory multiple myeloma (RRMM): Results from the CC-92480-MM-002 trial. ASH 2023;Abstract 1013.

Richardson PG et al. Mezigdomide plus dexamethasone in relapsed and refractory multiple myeloma. N Engl J Med 2023;389(11):1009-22. Abstract

Richardson PG et al. Mezigdomide (CC-92480), a potent, novel cereblon E3 ligase modulator (CELMoD), combined with dexamethasone (DEX) in patients (pts) with relapsed/refractory multiple myeloma (RRMM): Preliminary results from the dose-expansion phase of the CC-92480-MM-001 trial. ASH 2022;Abstract 1366.

Sandhu I et al. Mezigdomide (MEZI) plus dexamethasone (DEX) and bortezomib (BORT) or carfilzomib (CFZ) in patients (pts) with relapsed/refractory multiple myeloma (RRMM): Updated results from the CC-92480-MM-002 trial. ASH 2024;Abstract 1025.

van de Donk NWCJ et al. Iberdomide maintenance after autologous stem-cell transplantation in newly diagnosed multiple myeloma: An update from the phase 2 EMN26 trial. ASH 2025;Abstract 101.

Van Oekelen O et al. Iberdomide increases innate and adaptive immune cell subsets in the bone marrow of patients with relapsed/refractory multiple myeloma. Cell Rep Med 2024;5(6):101584. Abstract

Dr Alsina

Bal S et al. Efficacy and safety with extended follow-up in a phase 1 study of BMS-986393, a G protein-coupled receptor class C group 5 member D (GPRC5D)-targeted CAR T cell therapy, in patients (pts) with heavily pretreated relapsed/refractory (RR) multiple myeloma (MM). ASH 2024;Abstract 922.

Einsele H et al. Cilta-cel in lenalidomide-refractory multiple myeloma (CARTITUDE-4): An updated analysis including overall survival from an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol 2026;27(2):254-68. Abstract

Hansen DK et al. Comparison of standard-of-care idecabtagene vicleucel and ciltacabtagene autoleucel in relapsed/refractory multiple myeloma. J Clin Oncol 2025;43(13):1597-609. Abstract

Jagannath S et al. Long-term (≥5-Year) remission and survival after treatment with ciltacabtagene autoleucel in CARTITUDE-1 patients with relapsed/refractory multiple myeloma. J Clin Oncol 2025;43(25):2766-71. Abstract

Munshi NC et al. Idecabtagene vicleucel in relapsed and refractory multiple myeloma. N Engl J Med 2021;384(8):705-16. Abstract

Patel K et al. Phase 2 registrational study of anitocabtagene autoleucel for the treatment of patients with relapsed and/or refractory multiple myeloma: Updated results from iMMagine-1. ASH 2025;Abstract 256.

Rodriguez-Otero P et al. GPRC5D as a novel target for the treatment of multiple myeloma: A narrative review. Blood Cancer J 2024;14(1):24. Abstract