A Comprehensive Meta-Analysis of the Cardiovascular Adverse Effects of Bispecific Antibody Therapy in Hematologic Malignancies.

Introduction: Bispecific antibodies (BsAbs) are a promising and potent therapeutic intervention for relapsed or refractory (R/R) hematologic malignancies, including acute lymphoblastic leukemia (ALL), multiple myeloma (MM), and B-cell lymphomas. These recombinant molecules are designed to target two distinct antigens or epitopes. While BsAbs have shown significant efficacy in managing hematologic malignancies, toxicities must be carefully monitored and their safety profiles require further investigation. This meta-analysis investigates cardiovascular adverse effects associated with seven BsAbs across multiple clinical trials. Methods: A systematic literature review identified seven BsAbs, blinatumomab, elranatamab, epcoritamab, glofitamab, mosunetuzumab, talquetamab, and teclistamab, analyzing 25 clinical trials (Phase I-III) that included monotherapy regimens. The cardiovascular adverse events studied were arrhythmias, heart failure, blood pressure changes, and myocardial infarctions. A meta-analysis using the R meta package calculated proportions and 95% confidence intervals (CIs) and employed a random-effects model to assess heterogeneity. Results: Among 3215 patients, pooled analysis revealed significant findings with 13.6% cardiac arrhythmia (95% CI 10.1-18.2%, p = 0.05), 13.3% hypotension (95% CI 10-17.3%, p < 0.0001), 10.2% tachycardia (95% CI 7.6-13.5%, p = 0.0003), and 3.4% sudden death (95% CI 0-80%, p = 0.046). Less frequent events were hypertension (8%), acute myocardial infarction (1.5%), heart failure (1.4%), and atrial fibrillation (1.3%). Discussion: As BsAbs see increased use in R/R hematologic malignancies, cardiovascular complications must be closely monitored. This analysis highlights hypotension, cardiac arrhythmias, tachycardia, and sudden death as significant adverse effects. Although study heterogeneity and limited patient-level data may have influenced incidence estimates, these findings support routine cardiovascular monitoring and underscore the need for prospective studies to identify high-risk patients and optimize prevention and management strategies. Oncologists, cardiologists, and pharmacists should establish strategies for early detection and management to optimize patients' outcomes.