Infection risk associated with teclistamab in relapsed/refractory multiple myeloma: a systematic review and meta-analysis of clinical trial and real-world evidence

Background Teclistamab, a B-cell maturation antigen (BCMA) × CD3 bispecific antibody (BsAb), has shown remarkable efficacy in relapsed/refractory multiple myeloma (RRMM). However, its mechanism leads to profound hypogammaglobulinemia, making infection a critical concern. This systematic review and meta-analysis aimed to quantify the infectious burden and contrast outcomes between clinical trial and real-world evidence (RWE). Methods We systematically searched PubMed, Embase, Web of Science, and the Cochrane Library for studies reporting infection outcomes in RRMM patients treated with teclistamab. Pooled incidences of any-grade and grade ≥3 infections were calculated using a random-effects model. Subgroup analysis compared the pivotal MajesTEC-1 trial with multi-institutional RWE cohorts. Results Five studies encompassing 714 patients were included. The overall pooled incidence was 56.5% (95% CI: 43.1%–69.9%) for any-grade infections and 27.6% (95% CI: 21.0%–34.3%) for grade ≥3 infections. Subgroup analysis revealed a significantly higher risk in the clinical trial compared to RWE (Any-grade: 76.4% vs. 45.4%, p< 0.01; Grade ≥3: 44.8% vs. 22.8%, p<0.01). Infection-related mortality was reported in all cohorts, ranging from 0.9% to 7.3%, with COVID-19 and opportunistic pathogens (for example, Pneumocystis jirovecii) being prevalent. Significant heterogeneity was driven by variations in follow-up duration and intravenous immunoglobulin (IVIG) prophylaxis rates (range: 41.8%–81.3%). Conclusions Teclistamab is associated with a substantial and cumulative infectious burden. The lower infection rates in RWE may reflect shorter follow-up and evolving prophylactic strategies. Standardized infection surveillance, including regular IgG monitoring and consideration of IVIG replacement in patients with low IgG levels, may help optimize the safety of BCMA-directed bispecific therapies. Systematic Review Registration https://www.crd.york.ac.uk/prospero/ , identifier CRD420261297645.