Teclistamab 30mg/3ml solution for injection vials

Relapsed/refractory multiple myeloma (RRMM) remains a challenging condition with a need for more effective treatment options. There are ongoing clinical trials analyzing the effects of anti-B-cell maturation antigen (BCMA) bispecific antibodies (Abs) against RRMM with early, promising results. This study aims to systematically evaluate the safety and efficacy of anti-BCMA bispecific antibodies in patients with RRMM. PubMed, Embase, Web of Science, and the American Society of Hematology (ASH) website were searched for published evidence on the safety and efficacy of anti-BCMA bispecific Abs. Screening was performed using original clinical trials published in English, RRMM, and anti-BCMA-CD3 bispecific Abs as our inclusion criteria. Our search yielded a total of 2211 articles. After screening, we found 11 relevant clinical trials (five phase I, one phase I/II, two phase Ib, two phase II, one phase III). Across the trials, 910 patients with ages ranging from 32 to 82 years were analyzed. A majority of patients were exposed to and/or refractory to triple-class and penta-drugs (prior therapies ranged from 1 to 25). AMG-420, AMG-701, elranatamab, REGN5458, teclistamab (Tec), alnuctamab (ALNUC), and ABBV-383 are the seven anti-BCMA-CD3 bispecific Abs currently being assessed in clinical trials as monotherapy and in combination with immunomodulators/proteasome inhibitors against RRMM. Across the included trials, elranatamab demonstrated overall response rates (ORRs) of 61-64%, while teclistamab ranged from 40% to 78% depending on the regimen. ALNUC and ABBV-383 achieved ORRs of 51% and 57%, respectively. Among patients previously exposed to and/or refractory to anti-BCMA therapies (including antibody-drug conjugates and CAR-T cell therapy), ORRs were 54% for elranatamab and 40% for teclistamab. Incidence of cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS) was low with subcutaneous (SC) administration of tec, elranatamab, and ALNUC. Across the studies, no death was reported due to CRS, although it led to treatment discontinuation in one patient in AMG-420, two patients in AMG-701, and dose reduction in three patients in ABBV-383 trials. Our analysis of the trials revealed that bispecific Abs showed efficacy in RRMM, with CRS and hematologic toxicities being the most common adverse events, mostly low-grade and manageable. Based on the promising efficacy and safety of BCMA targeting bispecific Abs, these drugs are emerging as a new therapeutic option for patients with advanced and RRMM.

Abstract licence: CC BY

Background: 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. Methods: We manually searched 7 databases and identified 44 studies for quantitative analysis. Forest plots were created using R 4.1.x software. Results: Versus SOC, odds of ORR were higher with Talquetamab, Teclistamab, Elranatamab, and Linvoseltamab (5.73, 4.86, 3.84, 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). Linoseltamab and Elranatamab showed numerically longer OS relative to SOC ( HR 0.41, 0.24–0.70) and (HR 0.58, 0.43–0.78), 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 (68%); Teclistamab showed ORR of 61% with CRS 61% and Linvoseltamab showed ORR of 60% with CRS 51%. Cevostamab and Elranatamab had ORR 49% and 56% with CRS 61% and 52%, respectively. Conclusion: In RRMM, all bispecific antibodies showed superior ORR along with improved PFS as compared to SOC. Linoseltamab 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.

Abstract licence: CC BY

BackgroundDespite 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.MethodsWe 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.ResultsNine 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 ConclusionTeclistamab 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.

Abstract licence: CC BY-NC-ND

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.

Abstract licence: CC BY