Efficacy and safety of BCMA- or GPRC5D-directed CD3 bispecific antibodies in relapsed/refractory multiple myeloma: a systematic review and meta-analysis of prospective clinical trials and real-world studies

Objective BCMA- or GPRC5D-directed CD3 bispecific antibodies are important T-cell–redirecting therapies for relapsed/refractory multiple myeloma (RRMM). We evaluated their efficacy, safety, and certainty of evidence. Methods We searched the Cochrane Library, Embase, PubMed, Scopus, and Web of Science from inception to February 5, 2026. Prospective clinical trials and real-world studies of BCMA×CD3 or GPRC5D×CD3 bispecific antibodies in RRMM with extractable efficacy and safety data were included. Main efficacy outcomes were progression-free survival (PFS), stringent complete response (sCR), complete response (CR), complete response or better (≥CR), very good partial response or better (≥VGPR), and overall response rate (ORR). Safety outcomes included cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), infection, neutropenia, anemia, and thrombocytopenia. Single-arm proportional meta-analyses, sensitivity analyses, meta-regression, and subgroup analyses were performed using STATA/MP 18.0. Methodological quality and evidence certainty were assessed using MINORS and GRADE, respectively. Results Fifteen studies, including 17 independently extractable cohorts and 1,900 patients, were analyzed. The pooled PFS was 8.76 months (95% CI, 6.82–11.13). The pooled rates of sCR, CR, ≥CR, ≥VGPR, and ORR were 28.7%, 18.1%, 38.2%, 51.0%, and 65.9%, respectively. The pooled incidences of CRS, ICANS, infection, grade ≥3 infection, neutropenia, and grade ≥3 neutropenia were 67.5%, 9.7%, 60.3%, 38.3%, 54.7%, and 42.6%, respectively. MINORS showed moderate-to-high methodological quality. GRADE showed low-to-very low certainty of evidence. Conclusion BCMA- or GPRC5D-directed CD3 bispecific antibodies showed clinically meaningful antitumor activity in RRMM. However, current evidence is mainly from single-arm trials and retrospective real-world studies, and certainty of evidence remains low to very low. These findings should be interpreted cautiously, with particular attention to infection and neutropenia in clinical practice.