T-Cell Engagers Targeting BCMA, GPRC5D, or FcRH5 in Relapsed/Refractory Multiple Myeloma: The Landscape Beyond CAR-T Cell Therapy-A Systematic Review and Network Meta-Analysis

Relapsed/refractory multiple myeloma is marked by frequent triple-class refractoriness and poor survival, whereas bispecific antibodies targeting BCMA, GPRC5D, or FcRH5 show meaningful activity even in heavily pretreated and post-BCMA disease. This meta-analysis evaluates and compares the efficacy and safety of these agents in RRMM using direct and indirect evidence. We manually searched seven databases and identified 44 studies for quantitative analysis. Forest plots were created using R 4.1.1 software. Compared to Standard of care (SOC), the odds of Objective response rate (ORR) were higher with Talquetamab, Teclistamab, Elranatamab, and Linvoseltamab (5.73, 4.86, 3.84, and 2.63). PFS improved with Teclistamab (HR 0.50, 95% CI 0.36–0.55), Talquetamab (0.50, 0.36–0.55), Elranatamab (0.45, 0.36–0.55), and Linvoseltamab (0.23, 0.17–0.31). Linvoseltamab and Elranatamab showed numerically longer OS relative to SOC (HR 0.41, 0.24–0.70 and HR 0.58, 0.43–0.78, respectively), but numerically shorter OS with Teclistamab (HR 1.82, 1.37–2.42) and Talquetamab (HR 1.75, 1.20–2.57). In pooled single-arm data, Talquetamab had the highest ORR (72%) and CRS rate (68%); Teclistamab showed an ORR of 61% with a CRS rate of 61% and Linvoseltamab showed an ORR of 60% with a CRS rate of 51%. Cevostamab and Elranatamab had ORRs of 49% and 56% with CRS rates of 61% and 52%, respectively. In RRMM, all bispecific antibodies showed superior ORR along with improved PFS compared to SOC. Linvoseltamab and Elranatamab showed numerically longer OS relative to SOC, whereas Talquetamab and Teclistamab showed numerically shorter OS versus SOC, within the constraints of adjusted cross-trial comparisons.