Real-world evidence on infection risk in multiple myeloma treated with BiTEs and CAR-T cells: a meta-analysis

Abstract Background T-cell-redirecting therapies, including bispecific T-cell engagers (BiTEs) and chimeric antigen receptor T-cell (CAR-T) therapies, have substantially improved outcomes in relapsed or refractory multiple myeloma (RRMM). However, infectious complications remain a major safety concern, particularly in real-world settings, where patients are more heterogeneous than those enrolled in clinical trials. Methods We conducted a systematic review and meta-analysis of real-world retrospective studies evaluating severe (grade 3–4) infections in adult patients with RRMM treated with approved BiTEs or CAR-T cell therapies. Pooled event rates were estimated using random-effects models. Heterogeneity was explored through subgroup analyses, meta-regression, and sensitivity analyses. Results Sixteen studies encompassing 2,097 patients were included. Overall, 24.2% of patients developed grade 3–4 infections (pooled event rate 0.24; 95% CI, 0.21–0.28). Among BiTEs-treated patients ( n = 1,602), the pooled severe infection rate was 0.26 (95% CI, 0.23–0.30), with higher rates observed for BCMA-directed BiTEs (0.27) compared with GPRC5D-directed BiTEs (0.25). CAR-T cell therapies ( n = 495) were associated with a lower pooled infection rate (0.19; 95% CI, 0.12–0.27). Conclusions In real-world practice, severe infections affect approximately one in four patients receiving T-cell-redirecting therapies for RRMM. Observed differences in infection rates across platforms and targets should be interpreted with caution, as they derive from indirect comparisons in non-randomized, heterogeneous cohorts. Nevertheless, these data support incorporating patient frailty and prior infection history into therapeutic decision-making. CAR-T therapy, or GPRC5D-directed BiTEs when CAR-T is not feasible, may represent reasonable options in patients at higher infectious risk, within an individualized and context-dependent treatment strategy.