Real-World Evidence of Immunotherapy Sequencing in Multiple Myeloma: Durable Responses With BCMA-Targeting Bispecific...

T-cell-redirecting therapies (TCRTs), including bispecific antibodies (BsAbs) and chimeric antigen receptor-T-cell therapy targeting B-cell maturation antigen (BCMA) or G-protein-coupled receptor class C group 5 member D (GPRC5D), have demonstrated significant efficacy in patients with relapsed/refractory multiple myeloma (RRMM). However, relapse remains common, highlighting the need for optimized TCRT sequencing strategies.

This retrospective multicenter study evaluated the safety and efficacy of BCMA-targeting BsAbs following prior treatment with GPRC5D-targeting BsAbs in RRMM patients.

A total of 26 patients were included, with a median follow-up of 20.35 months. The overall response rate was 58%, with a median progression-free survival (PFS) of 6.8 months and a median overall survival of 15.9 months. Responders demonstrated significantly longer PFS compared to nonresponders (not reached vs. 3.5 months, P < .001). The safety profile remained consistent with previous BCMA-targeting BsAbs, with cytokine release syndrome occurring in 50% of patients--none of whom experienced grade ≥ 3 events--and 38% developing grade ≥ 3 infections.

BCMA-targeting BsAbs offer an effective and well-tolerated treatment option for patients who have progressed after GPRC5D-targeting BsAbs, supporting the feasibility of this sequential approach as a promising strategy.