Infections following bispecific antibodies in myeloma: a systematic review and meta-analysis

Reynolds, G; Cliff, ERS; Mohyuddin, GR; Popat, R; Midha, S; Ng Liet Hing, M; Harrison, SJ; Kesselheim, AS; Teh, BW

Author(s): Reynolds, G; Cliff, ERS; Mohyuddin, GR; Popat, R; Midha, S; Ng Liet Hing, M; Harrison, SJ; Kesselheim, AS; Teh, BW;
Details: Publication Year 2023,Volume 7,Issue #19,Page 5898-5903
Journal Title: Blood Advances
Publication Type: Review
Abstract: 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 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.
Publisher: American Society of Hematology
Keywords: Humans; *Multiple Myeloma/drug therapy/pathology; *Antibodies, Bispecific/adverse effects; B-Cell Maturation Antigen/therapeutic use; Immunotherapy; T-Lymphocytes; CD3 Complex
Department(s): Infectious Diseases; Clinical Haematology
PubMed ID: 37467036
Publisher's Version: https://doi.org/10.1182/bloodadvances.2023010539
Open Access at Publisher's Site: https://doi.org/10.1182/bloodadvances.2023010539
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2023-12-05 12:49:38

Last Modified: 2023-12-05 12:50:18