Reynolds, GemmaCliff, EdwardMohyuddin, Ghulam RehmanPopat, RakeshMidha, ShonaliLiet Hing, Melissa NgHarrison, Simon J.Kesselheim, AaronTeh, Benjamin W.2023-12-202023-09-29Reynolds, Gemma, Edward Cliff, Ghulam Rehman Mohyuddin, Rakesh Popat, Shonali Midha, Melissa Ng Liet Hing, Simon J. Harrison et al. "Infections following bispecific antibodies in myeloma: a systematic review and meta-analysis." Blood Advances 7, no. 19 (2023): 5898-5903. DOI: 10.1182/bloodadvances.20230105392473-95292473-9537https://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37377563Bispecific 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 G protein–coupled receptor 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 patients with myeloma treated with bispecific antibodies was conducted to better characterize the infection risks. A literature search used 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%, whereas the prevalence of grade ≥3 infections was 24%. Patients who were treated with BCMA-targeted bispecifics had significantly higher rates of grade ≥3 infections than non-BCMA bispecifics (25% vs 20%). Similarly, patients treated with bispecifics in combination with other agents had significantly higher rate of all-grade infection than those receiving monotherapy (71% vs 52%). In observational studies (n = 293), excluded from the primary analysis to ensure no overlap with patients in clinical trials, 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.en-USHematologyJournal Article2023-12-2010.1182/bloodadvances.2023010539