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.