Subsequent CAR-T and engineered antibody for relapsed/refractory multiple myeloma following BCMA-targeted treatment:...

Relapse following B-cell maturation antigen (BCMA)-directed therapies represents a critical challenge in relapsed/refractory multiple myeloma (R/R MM). We performed a systematic review and meta-analysis of 34 studies (n = 1280) published between 2020 and 2025 to evaluate salvage CAR-T versus engineered antibody therapies post-BCMA exposure. The pooled overall response rate (ORR) was 60%. CAR-T therapy achieved significantly superior ORR compared to antibody-based approaches (77% vs 52%; p < 0.0001), with comparable complete response rates. While incidences of cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome were similar, grade ≥3 cytopenias were more frequent with CAR-T. Notably, GPRC5D-targeted CAR-T yielded higher ORRs than BCMA-targeted constructs (86% vs 66%; p = 0.0006). Furthermore, patients with prior exposure to BCMA bispecific antibodies exhibited lower response rates compared to those with prior CAR-T exposure (71% vs 86%; p = 0.0404). In addition, studies with a median interval of ≥10 months demonstrated significantly higher ORRs than those with <10 months (70% vs 50%; p = 0.0146). In conclusion, GPRC5D CAR-T demonstrates superior efficacy to engineered antibodies in the post-BCMA setting. These findings support prioritising earlier CAR-T use and underscore the importance of antigen selection in optimising treatment sequencing.