Cardiovascular Adverse Events Associated With Bispecific T-Cell Engager Therapy

Although some cancer immunotherapies have been linked to increased cardiovascular risk, data on T-cell engager (TCE) therapy-associated cardiovascular complications remain limited.

This study sought to characterize the incidence and factors associated with cardiovascular events (CVEs) and mortality during TCE therapy.

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.

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.

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.