BackgroundTeclistamab, 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).MethodsWe 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.ResultsFive 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%).ConclusionsTeclistamab 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 Registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD420261297645.
Huang et al. (Wed,) studied this question.