Meta-analysis of the cardiovascular adverse effects of bispecific antibodies in malignant hematology therapies.

Abstract

e14503 Background: Bispecific antibodies (BsAbs), recombinant molecules that target two distinct antigens or epitopes, are a promising therapeutic option for relapsed or refractory (R/R) hematologic malignancies, including acute lymphoblastic leukemia (ALL), multiple myeloma (MM), and B-cell lymphoma. While BsAbs have shown significant efficacy in managing hematologic malignancies, toxicities must be carefully monitored and their safety profiles require further investigation. Notably, cardiovascular adverse effects have not been extensively studied despite reported incidents in BsAbs such as blinatumomab and teclistamab. This meta-analysis aims to investigate the cardiovascular toxicities associated with seven BsAbs across multiple clinical trials. Methods: A systematic literature review identified seven BsAbs and their associated randomized control clinical trials. The BsAbs in this analysis were blinatumomab, elranatamab, epcoritamab, glofitamab, mosunetuzumab, talquetamab, and teclistamab and only monotherapy regimens were included. 37 clinical trials were analyzed (6 Phase I, 12 Phase I/II, 15 Phase II, 1 Phase II/III, 3 Phase III). Cardiovascular adverse events that were analyzed include arrhythmias, heart failure, blood pressure changes, and myocardial infarctions. All cardiac adverse events were pooled and studied collectively. A meta-analysis was performed using the R meta package. Proportions and 95% confidence intervals (CI) were calculated for each study. A random-effects model was utilized. Heterogeneity was assessed using the I 2 statistic. Results: A total of 3758 patients were included. Significant occurrence rates were 10.2% tachycardia (95% CI 7.6-13.5%, p < 0.05, I 2 = 64.9%), 12.6% cardiac arrhythmias (95% CI 7.8-19.7%, p = 0.05, I 2 = 50.1%), and 13.3% hypotension (95% CI 10-17.3%, p < 0.05, I 2 = 76.9%). Other rates were 1.5% acute myocardial infarction (95% CI 0.7-3.1%, p = 0.5, I 2 = 0%), 1.3% atrial fibrillation (95% CI 0.4-4.4%, p = 0.062, I 2 = 52.5%), 8% hypertension (95% CI 5.8-11%, p = 0.19, I 2 = 27.5%), and 1.4% heart failure (95% CI 0.3-5.8%, p = 0.085, I 2 = 48.3%). Blinatumomab was the most represented BsAb during analysis, followed by mosunetuzumab, elranatamab, and teclistamab. Conclusions: As BsAbs have demonstrated promising efficacy and increased use in the treatment of R/R hematologic malignancies, a wide variety of cardiac toxicities have been observed in these patients and more data on these toxicities are documented. This meta-analysis has identified tachycardia, cardiac arrhythmias, and hypotension as the most significant cardiac adverse events in a pooled analysis of multiple BsAbs. Practicing oncologists, cardiologists, and pharmacists need not only to be aware of these potential toxicities, but also to establish strategies for cardiac monitoring, prevention and management in order to provide quality care to cancer patients.