Outcomes of CAR T-cell Therapy and Bispecific Antibodies as Single-Modality and Sequential Strategies in Relapsed/Refractory Multiple Myeloma.

UNLABELLED: We explored single or consecutive chimeric antigen receptor (CAR) T and bispecific antibody (BsAb) treatment modalities as correlates of clinical outcomes, by complementary bias-correction analysis of a retrospective multicenter study of 640 patients with relapsed/refractory multiple myeloma. The sequential use of both modalities seemed to yield the most favorable survival trajectories. Initiating treatment with CAR T [idecabtagene vicleucel (ide-cel), ciltacabtagene autoleucel (cilta-cel), cesnicabtagene autoleucel (cesni-cel)] was associated with longer remission. However, mortality from early progression was similar regardless of initial modality, suggesting that resistance may negate initial efficacy difference. On the product level, the benefit of CAR T seemed to be driven by cilta-cel and cesni-cel, whereas BsAbs showed at least comparable outcomes with ide-cel. These exploratory findings highlight the critical importance of treatment sequencing in optimizing long-term outcomes and underscore the need for equitable and timely access to both modalities across healthcare systems.

SIGNIFICANCE: In this real-world cohort, initiating treatment with CAR T was associated with longer remission, and sequential immunotherapy incorporating both modalities yielded the most favorable outcomes. However, early treatment failure negated initial efficacy differences between modalities. These findings provide a rationale for prospective sequencing trials and equitable access to both treatments. See related commentary by Banerjee, p. 650.