Case Discussion: Treatment Sequencing After Prior BCMA-Directed Therapy 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.