Bispecific antibodies in the treatment of relapsed refractory multiple myeloma: A meta analysis.

Abstract

e19529 Background: Relapsed/refractory multiple myeloma (RRMM) includes relapse after response orprogression within 60 days of the last regimen, and many patients become triple‐class refractory(PI, IMiD, and anti‐CD38 refractory) with historical median overall survival of about 1 year.Bispecific antibodies (bsAbs) targeting B-Cell Maturation Antigen (BCMA) (Teclistamab,Elranatamab), GPRC5D (Talquetamab), or FcRH5 (Cevostamab) have shown substantialactivity even in heavily pretreated, post‐BCMA patients. However, survival comparisons acrossindividual bsAbs are limited by heterogeneous populations, prior BCMA exposure, and evolvingsequencing (e.g., bsAbs as CAR‐T bridging). This meta-analysis therefore aims to provide directand indirect comparative data on the efficacy and safety of bsAbs in RRMM. Methods: We manually searched major medical databases and identified 28 studies for pooledsingle‐arm analyses of bsAbs (5 Cevostamab, 5 Teclistamab, 5 Elranatamab, 10 Talquetamab),plus 7 additional studies for indirect bsAbs versus standard‐of‐care comparisons and forest plotswere created using R software. Results: The pooled objective response rate (ORR) was 0.72 (95% CI 0.68–0.75) forTalquetamab, 0.55 (0.39–0.70) for Elranatamab, 0.60 (0.56–0.65) for Teclistamab, and 0.49(0.24–0.74) for Cevostamab. The pooled complete response rate (≥CR) was 0.33 (0.27–0.40)for Talquetamab, 0.32 (0.19–0.49) for Elranatamab, 0.23 (0.13–0.37) for Teclistamab, and 0.14(0.03–0.43) for Cevostamab. The pooled incidence of cytokine release syndrome (CRS) was0.66 (0.57–0.73) for Talquetamab, 0.52 (0.32–0.71) for Elranatamab, 0.57 (0.50–0.64) forTeclistamab, and 0.69 (0.48–0.84) for Cevostamab. The pooled incidence of ICANS was 0.10(0.07–0.14) for Talquetamab, 0.11 (0.01–0.58) for Elranatamab, 0.10 (0.05–0.17) forTeclistamab, and 0.18 (0.09–0.35) for Cevostamab. Elranatamab was associated with asignificantly higher ORR versus (SOC) (OR 3.84; 1.85–7.96), whereas Talquetamab andTeclistamab showed numerically higher but not statistically significant ORR compared with SOC(OR 5.71; 0.66–49.34) and (OR 4.12; 0.64–26.74) respectively. Conclusions: Talquetamab has the highest pooled ORR and ≥CR among the bispecifics, thoughall four show meaningful activity with similar CRS and ICANS rates. Elranatamab is the onlyagent with a statistically superior ORR versus standard of care; Talquetamab and Teclistamabconfer only numerically higher, non‐significant ORR improvements.