Comparative efficacy and safety of BCMA-targeted CAR T cells and BiTEs in relapsed/refractory multiple myeloma: a meta-analysis of interventional and real-world studies.

Abstract

Despite therapeutic advances, multiple myeloma (MM) remains incurable, especially in relapsed/refractory (R/R) cases. B-cell maturation antigen (BCMA) is a key target for novel immunotherapies, including chimeric antigen receptor T-cell (CAR-T) therapies and bispecific T-cell engagers (BiTEs), which vary in efficacy, toxicity, and accessibility. To compare the efficacy and safety of BCMA-directed CAR-T therapies and BiTEs in R/R MM through a systematic review and meta-analysis. We systematically searched PubMed, Embase, and the Cochrane Library up to October 2, 2024, for studies evaluating BCMA-directed CAR-T or BiTEs therapies in R/R MM. Twenty-six studies comprising 2,246 patients were included. A random-effects meta-analysis and meta-regression were performed to assess pooled efficacy and safety outcomes and examine the impact of CAR-T constructs and patient-level characteristics. CAR-T therapies showed a higher overall response rate (ORR) of 84% and CR/stringent CR (CR/sCR) of 55%, compared to 65% and 41%, respectively, for BiTEs. Dual-targeted CAR-T therapies (e.g., anti-BCMA + anti-CD38/CD19) had the highest efficacy (ORR 92%). CAR-T was associated with more hematologic toxicity and cytokine release syndrome, while BiTEs had fewer severe events but higher infection rates. Meta-regression confirmed CAR-T significantly outperformed BiTEs. Unlike previous analyses, this study integrates interventional and real-world data, evaluates dual-target CAR-Ts, and offers detailed product- and subgroup-level comparisons. BCMA-targeted CAR-T therapies yield deeper responses but greater toxicity. BiTEs offer safer, though less potent, alternatives, supporting more personalized decisions in BCMA-directed immunotherapy for MM.