Salvage outcomes with teclistamab after BCMA-directed therapy failure in relapsed/refractory multiple myeloma: a systematic review and meta-analysis.

BACKGROUND: Despite advances in treatments multiple myeloma remains a therapeutically challenging disease. Although BCMA-directed therapies have improved outcomes, no standard exists after relapse. Teclistamab, a BCMA × CD3 bispecific antibody, redirects T cells to lyse myeloma cells and may overcome resistance to prior BCMA-targeting therapies. METHODS: We conducted a systematic review and meta-analysis according to PRISMA guidelines, searching major databases from inception through November 2025. Adults with relapsed/refractory multiple myeloma (RRMM) who received teclistamab after prior BCMA-directed therapy (BDT) were included. Primary outcomes were overall response rate (ORR), complete response (CR) rate, very good partial response (VGPR), and partial response (PR). Secondary outcomes were progression-free survival (PFS), overall survival (OS), and one-year overall survival (1-year OS). Response proportions were pooled using random-effects models, evidence was assessed using the GRADE, Kaplan-Meier curves were reconstructed to compare the survival between BDT-exposed and BDT-naive cohorts. RESULTS: Nine observational studies including 718 BDT-exposed patients were included., Teclistamab achieved a pooled ORR of 56% (95% CI: 50-63; I²=73%), with a CR rate of 22% (95% CI: 17%-27%; I² = 0%). VGPR rate was 20% (95% CI: 15%-27%). Among prior CAR-T recipients (n = 371), ORR was 58% (95% CI: 47%-69%; CR 29%), while prior ADC recipients (n = 114) had an ORR of 64% (95% CI: 50%-76%; CR 19%). BDT-exposed patients had a median PFS of 101 days compared with 220 days in BDT-naive patients (HR for BDT-naive vs. exposed = 0.47, 95% CI: 0.39-0.56; p < 0.01), whereas median OS was comparable between groups (437 days in each group; HR = 1.00; p = 0.997). Infections occurred in 44.6% of patients, any-grade CRS in 57.9% (grade ≥3, 1.3%), neutropenia in 32.3%. The overall GRADE certainty of evidence was low to very low across most outcomes due to high risk of bias, heterogeneity, and indirectness. CONCLUSION: Teclistamab shows meaningful activity after BCMA therapy failure and may represent a salvage option. However, efficacy estimates must be interpreted with caution given the low to very low certainity of evidence. Prospective biomarker-stratified trials are needed to optimize BCMA-targeting sequences and identify patients most likely to benefit.