Adverse events in Relapsed/Refractory multiple myeloma (RRMM) patients receiving bi-specific T-cell antibodies (BsAbs): A systematic review and meta-analysis of real-world evidence Free

Introduction: Bi-specific T-cell antibodies (BsAbs)—a type of immunotherapy used to treat relapsed/refractory multiple myeloma (RRMM)—bind to target molecules on MM and T cells simultaneously, resulting in T-cell activation and death of MM cells. Based on evidence from clinical trials, real-world studies help contextualize the risk of adverse events in a more diverse population receiving treatment in routine practice.

Methods: On June 1, 2025, we conducted a literature search in PubMed and Embase using controlled vocabularies and keywords related to MM, BsAbs, teclistamab, talquetamab, and elranatamab. Title/abstract screening and full-text review were conducted. Articles published in peer-reviewed journals that assessed adverse events in RRMM patients receiving BsAbs (teclistamab, talquetamab, and elranatamab) in the real-world settings were included. Descriptive statistics were used for qualitative summary. In meta-analysis, a random-effects model synthesized rates of adverse events. Meta-regression was used to assess if rates of adverse events varied by study-level factors indicating prior treatment burden (proportion of patients with a history of CAR-T, proportion of triple-class refractory patients, and median line of prior therapy) or aging (median age and proportion of patients with ECOG PS ≥2).

Results: Seventeen articles were included for the systematic review (16 for meta-analysis). Nine studies were conducted in the US, 6 were in Europe, and 2 were international multicenter studies. Overall, 12, 2, and 1 study focused on teclistamab, talquetamab, and elranatamab, respectively; moreover, 2 studies pooled teclistamab and elranatamab for investigation, with 1 of them additionally investigating talquetamab. The sample size ranged from 25 to 385 (median: 72), with a total of 2,093 RRMM patients. The median age ranged from 63 to 70 years (median: 67 years). Cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), infection, and hematotoxicity (anemia, neutropenia, thrombocytopenia, leukopenia) were major types of adverse events reported in these articles (CRS: 15, ICANS: 15, infection: 10, hematotoxicity: 7). In meta-analysis, rates of CRS in teclistamab users ranged from 32% to 89% across different articles, and the synthesized rate was 56% (95% CI=50% - 63%, Cochran P<0.01, I²=78.8%); the CRS rate of talquetamab users ranged from 66% to 86% (synthesized rate=74%, 95% CI=63% - 83%, Cochran P=0.18, I²=42.4%). The rate of ICANS in teclistamab users varied from 3% to 15% across different studies (synthesized rate=9%, 95% CI=7% - 12%, Cochran P=0.02, I²=53.8%), and the rate varied between 4% and 9% for talquetamab users (synthesized rate=7%, 95% CI=4% - 12%, Cochran P=0.74, I²=0%). Seven studies reported CRS and ICANS by grade for teclistamab users (≥ grade 3: CRS: 0-4.5%, ICANS: 0-7.4%), and 2 studies reported the grade for talquetamab users (≥ grade 3: CRS: 0-5.1%, ICANS: 0-1.5%). For teclistamab users, the synthesized rate of infection, anemia, neutropenia, thrombocytopenia, and leukopenia was 43%, 64%, 38%, 40%, and 37%, respectively. Pooling teclistamab and elranatamab as one category (BCMA-targeted T-cell antibodies) did not change the synthesized estimates substantially in meta-analysis. Meta-regression for teclistamab suggested a significant correlation of CRS with proportion of patients with a history of CAR-T (coefficient [per 5%]=2.0%, 95% CI=0.4% - 3.5%, 7 studies) and median lines of prior therapy (coefficient=17.2%, 95% CI=2.0% - 32.5%, 10 studies). The meta-regression also suggested a positive and significant correlation between proportion of triple-class refractory MM patients and rate of anemia, neutropenia, and thrombocytopenia in teclistamab users. In meta-regression for BCMA-targeted T-cell antibodies (teclistamab and elranatamab), ECOG ≥2 was positively associated with anemia.

Conclusions: In the meta-analysis, about half of RRMM patients using teclistamab can experience CRS, and about three-fourths of talquetamab users can have CRS. ICANS is not frequently observed in teclistamab and talquetamab users. In teclistamab users, prior treatment burden could be positively associated with CRS and hematotoxicity. The meta-regression did not identify any study-level factors associated with infection in BsAbs users. The substantial statistical heterogeneity in teclistamab users and the small number of studies investigating talquetamab are limitations of this study.