Cesar Rodriguez

Dr. Harsh Parmar presents results from the phase 3 MAJESTEC-3 trial evaluating the combination of teclistamab and daratumumab versus standard daratumumab-based regimens in patients with relapsed/refractory multiple myeloma (R/R MM) who had received one to three prior lines of therapy. He reviews the study design, eligibility criteria, and key efficacy outcomes, demonstrating substantial improvements in progression-free survival, overall response rate, depth of response, minimal residual disease negativity, and overall survival with the teclistamab-based regimen. Dr. Parmar also discusses the safety profile, highlighting rates of neutropenia, infections, cytokine release syndrome, and neurotoxicity, while emphasizing that cytokine release syndrome events were generally low grade and manageable with appropriate supportive care. The presentation concludes with practical considerations for infection prophylaxis, including intravenous immunoglobulin and antimicrobial prophylaxis, as well as the benefits of response-adapted dosing strategies to improve tolerability while maintaining the clinical efficacy of teclistamab-based therapy in relapsed/refractory multiple myeloma.

Following the MAJESTEC-3 presentation, the faculty discuss how the trial findings may influence the evolving treatment landscape for relapsed/refractory multiple myeloma (R/R MM). Dr. Harsh Parmar, Dr. Gurbakhash Kaur, Dr. Cesar Rodriguez, and Dr. Prashant Kapoor examine the potential role of earlier teclistamab plus daratumumab therapy while considering its impact on future treatment options, particularly subsequent BCMA-directed CAR-T cell therapy. The panel discusses challenges related to sequencing after prior BCMA exposure, the importance of preserving future therapeutic options, and the need for emerging strategies such as alternative antigen targets and next-generation cellular therapies. Faculty also review practical considerations including infection risk, the role of intravenous immunoglobulin and antimicrobial prophylaxis, patient selection, frailty, caregiver support, and the balance between continuous therapy and time-limited treatment approaches. The discussion concludes that treatment decisions should remain highly individualized, incorporating disease characteristics, patient preferences, access to specialized care, and evolving clinical evidence as the sequencing of BCMA-directed therapies continues to develop in relapsed/refractory multiple myeloma.

The faculty discuss treatment sequencing for a patient with relapsed/refractory multiple myeloma (R/R MM) who has experienced disease progression following prior BCMA-directed therapy. Dr. Harsh Parmar outlines an individualized approach based on the type of prior BCMA therapy received, emphasizing the importance of selecting a different therapeutic target after CAR-T therapy and considering non-immunotherapy regimens, cellular therapies, or clinical trials following progression on a BCMA bispecific antibody. Dr. Cesar Rodriguez expands on key factors influencing sequencing decisions, including the interval since prior BCMA-directed therapy, T-cell fitness, disease burden, and the potential need for conventional chemotherapy to reduce tumor burden before subsequent immunotherapy. The panel also discusses emerging concepts such as mechanisms of resistance, including T-cell exhaustion and BCMA antigen loss, the need for predictive biomarkers to guide treatment selection, and ongoing knowledge gaps regarding optimal sequencing and retreatment strategies. The discussion underscores the evolving evidence base needed to optimize care for patients with relapsed/refractory multiple myeloma following prior BCMA-directed therapy.

The faculty discuss treatment selection for a fit patient with relapsed/refractory multiple myeloma (R/R MM) who is eligible for both CAR-T cell therapy and BCMA bispecific antibodies and has access to a certified CAR-T treatment center. Dr. Gurbakhash Kaur explains why CAR-T cell therapy would be the preferred approach for this patient, emphasizing the importance of disease control with appropriate bridging therapy while awaiting cell collection and manufacturing. The panel also discusses how disease tempo, patient preference, and logistical considerations influence treatment planning. Dr. Ridhi Gupta underscores the value of early referral to a CAR-T center before initiating BCMA-directed therapy to preserve treatment options and facilitate timely T-cell collection. The discussion concludes by highlighting the importance of identifying appropriate candidates early in the disease course, coordinating care between community and academic centers, and using periods of stable disease as an opportunity to optimize treatment planning for relapsed/refractory multiple myeloma.