Cardiovascular adverse events associated with bispecific antibodies in Relapsed/Refractory hematologic malignancies: A comprehensive systematic review and meta-analysis

Abstract

Abstract Introduction: Bispecific antibodies (BsAbs), targeting two distinct antigens, offer promising treatment for relapsed/refractory hematologic malignancies such as ALL, MM, and B-cell lymphoma. Despite their efficacy, cardiovascular toxicities remain underreported. This meta-analysis evaluates cardiovascular adverse events linked to seven BsAbs across multiple clinical trials. Methods: A systematic search of MEDLINE, EMBASE, and CENTRAL was conducted for studies up to August 2025. Meta-analysis was performed using Stata 18.0, and ROBS 2.0 assessed risk of bias. Result: In this meta-analysis, a total of 1647 clinical trials were screened, and all 37 studies were included in the final analysis. The analysis involved a total of 3758 patients, although the gender distribution (male and female) was not specified in the available data. The study included seven bispecific antibodies (BsAbs): blinatumomab, mosunetuzumab, elranatamab, epcoritamab, glofitamab, talquetamab, and teclistamab. These therapies were analyzed for their associated cardiovascular adverse events (CVAEs). The results revealed several significant cardiovascular toxicities. Tachycardia occurred in 10.2% of patients (95% CI 7.6-13.5%, p<0.05, I²=64.9%), cardiac arrhythmias were reported in 12.6% (95% CI 7.8-19.7%, p=0.05, I²=50.1%), and hypotension in 13.3% of patients (95% CI 10-17.3%, p<0.05, I²=76.9%). Additionally, acute myocardial infarction (AMI) occurred in 1.5% (95% CI 0.7-3.1%, p=0.5, I²=0%), atrial fibrillation (AFib) in 1.3% (95% CI 0.4-4.4%, p=0.062, I²=52.5%), hypertension in 8% (95% CI 5.8-11%, p=0.19, I²=27.5%), and heart failure (HF) in 1.4% (95% CI 0.3-5.8%, p=0.085, I²=48.3%). BsAb-specific findings indicated that blinatumomab was associated with a higher risk of disseminated intravascular coagulation (DIC), with a relative reporting odds ratio (ROR) of 3.02. Furthermore, teclistamab exhibited a disproportionately high risk of myocarditis and shock, with ROR values of 25.70 and 3.63, respectively. These results underscore the need for tailored monitoring and management strategies based on the specific bispecific antibody being administered. Conclusion: While bispecific antibodies (BsAbs) show promising results in managing R/R hematologic malignancies, their use can lead to significant cardiac adverse effects, including tachycardia, arrhythmias, and hypotension. To mitigate these risks, a multidisciplinary approach—incorporating vigilant cardiac monitoring, preventive strategies, and prompt intervention—is essential for optimizing patient care and treatment success. Risk of Bias was relatively low.