Real-world incidence of severe infections in multiple myeloma patients receiving bispecific antibodies: a meta-analysis

Bispecific antibodies (BiTEs) have transformed the therapeutic landscape of relapsed/refractory multiple myeloma (RRMM), offering deep and durable responses even in heavily pretreated patients. However, their use carries a substantial infectious risk due to the huge immunosuppression, particularly hypogammaglobulinemia, induced by T-cell-redirecting therapy. To define the real-world incidence of grade 3–4 infections, we conducted a systematic review and meta-analysis of retrospective studies including RRMM patients treated with BiTEs currently approved for clinical use.Ten studies encompassing 1,373 patients were analyzed using a random-effects model of pooled proportions. The overall rate of grade 3–4 infections was 25% (95% CI, 0.22–0.30) after a median follow-up of 8.3 months, with moderate heterogeneity (I²=52.9%). Subgroup analyses showed comparable pooled event rates for teclistamab - anti-CD3/BCMA − (0.26; 95% CI, 0.22–0.31) and talquetamab - anti-CD3/GPRC5D (0.23; 95% CI, 0.14–0.33). Meta-regression revealed a counterintuitive inverse association between infection rates and both the mean number of prior therapy lines (p = 0.002) and prior BCMA exposure (p = 0.0019), likely because in real-world practice, clinicians tend to select fitter and more immunologically stable patients for BiTEs therapy.In summary, approximately one in four RRMM patients receiving BiTEs in clinical practice experiences a severe infection. These findings underscore the need for proactive infection monitoring and standardized preventive measures, including immunoglobulin replacement, antimicrobial prophylaxis, and vaccination, to ensure the safe and effective integration of BiTEs into routine MM care.