Infections After Bispecific Antibodies in Patients With Myeloma

Bispecific antibodies, a novel immunotherapy with promising efficacy against multiple myeloma, form immune synapses between T-cell surface marker CD3 and malignant cell markers, including B-cell maturation antigen (BCMA), FcRH5, and GPRC5D. These bispecific antibodies so effectively deplete plasma cells (and to some extent T-cells) that patients are at increased risk of developing infections. A systematic review and meta-analysis of infections in published studies of myeloma patients treated with bispecific ntibodies was conducted to better characterize the infection risks. A literature search utilized MEDLINE, EMBASE, and Cochrane to identify relevant studies between inception and February 10, 2023, including major conference presentations. Phase 1b-3 clinical trials and observational studies were included. Sixteen clinical trials comprising 1666 patients were included. Median follow-up was 7.6 months and 38% of the cohort had penta-drug refractory disease. Pooled prevalence of all-grade infections was 56% (95% confidence interval [CI]: 0.48–0.65), while the prevalence of grade ≥3 infections was 24% (95%CI: 0.19–0.29). Patients who were treated with BCMA-targeted bispecifics had significantly higher rates of grade ≥3 infections than non-BCMA bispecifics (25% vs. 20%, p<0.01). Similarly, patients treated with bispecifics in combination with other agents had a higher rate of all-grade infection than those receiving monotherapy (71% vs. 52%, p<0.01). In observational studies (n=293), excluded from the primary analysis to ensure no overlap with clinical trial patients, several infections classically associated with T-cell depletion were identified. This systematic review identifies BCMA-targeted bispecifics and bispecific combination therapy as having higher infection risk, requiring vigilant infection screening and prophylaxis strategies.