Cardiovascular Adverse Events Associated With Bispecific T-Cell Engager Therapy

Background Although some cancer immunotherapies have been linked to increased cardiovascular risk, data on T-cell engager (TCE) therapy–associated cardiovascular complications remain limited. Objectives This study sought to characterize the incidence and factors associated with cardiovascular events (CVEs) and mortality during TCE therapy. Methods We conducted a dual-center retrospective study of patients with cancer treated with TCEs between 2016 and 2024. The cumulative incidence of on-treatment CVEs (heart failure, arrhythmias, myocardial infarction, stroke) and cardiovascular mortality was evaluated using Fine-Gray competing-risks models incorporating time-dependent grade ≥2 cytokine-release syndrome (CRS) and/or immune effector cell–associated neurotoxicity syndrome (ICANS). Factors associated with all-cause mortality were assessed using Cox models including CVEs as a time-dependent covariate. Results Among 567 patients (median age 67 years [Q1-Q3: 57-75]; 46.0% female), 25.9% had preexisting cardiovascular disease. The most common malignancies were multiple myeloma (40.9%) and acute lymphoblastic leukemia (35.6%). The restricted mean follow-up was 248 days (range: 0-973), during which 65 CVEs occurred (cumulative incidence 10.4%; 95% CI: 8.1-13.1), most commonly new left ventricular dysfunction (2.3%) and new-onset atrial fibrillation (2.1%). Cardiovascular mortality was rare (2 cases, 0.4%). Coronary artery disease was the only baseline variable independently associated with CVEs, whereas development of grade ≥2 CRS and/or ICANS was associated with a significant time-dependent increase in CVE risk. CVEs were significantly associated with higher all-cause mortality, independent of baseline clinical factors and TCE agent. Conclusions TCE therapy demonstrates a favorable cardiovascular safety profile overall, yet cardiovascular complications during therapy are associated with markedly increased mortality risk. Patients with preexisting coronary artery disease and those who develop high-grade CRS and/or ICANS represent high-risk groups that may benefit from intensified cardiovascular assessment and monitoring.