Cancer treatment-related cardiovascular toxicity according to the ESC definition in patients receiving CAR T-cell therapy

Background

Chimeric antigen receptor (CAR) T-cell therapy has substantially improved outcomes in refractory hematologic malignancies but may cause cardiovascular complications, particularly in the context of cytokine release syndrome (CRS). Real-world data on incidence, severity, and prognostic relevance of cancer therapy-related cardiovascular toxicity (CTR-CVT) defined by the 2022 ESC cardio-oncology guidelines remain in the context of CAR-T cell therapy limited.

Methods

This retrospective single-center study includes 104 patients treated with CAR T-cells between 09/2019 and 02/2024 for acute lymphoblastic leukemia, non-Hodgkin lymphoma and multiple myeloma. The primary endpoint was new-onset CTR-CVT during hospital stay, defined as cancer therapy-related cardiac dysfunction (CTRCD), arrhythmia, myocardial infarction, cardiogenic shock, or cardiovascular death. Clinical characteristics, biomarkers, echocardiographic parameters, CRS/ICANS severity, and survival outcomes were analyzed.

Results

Fifty-two patients (50%) met criteria for CTR-CVT, predominantly due to asymptomatic biomarker elevation. CTRCD occurred in 48.1%, whereas clinically significant events were rare: three patients developed symptomatic CTRCD, one experienced cardiogenic shock, and no myocardial infarctions or cardiovascular deaths were observed. Cardiovascular events occurred early and were associated with higher-grade CRS and ICANS, as well as elevated inflammatory markers. Reduced baseline left ventricular ejection fraction, elevated systolic pulmonary artery pressure, impaired performance status, and beta-blocker use were associated with increased CTR-CVT risk. Survival was numerically lower in patients with CTR-CVT but did not reach statistical significance.

Conclusion

Although half of patients fulfilled ESC criteria for CTR-CVT, clinically relevant cardiac events after CAR T-cell therapy were uncommon. These findings suggest potential overclassification driven by biomarker elevations and underscore the importance of emphasizing clinical relevance when assessing cardiotoxicity in CAR T-cell recipients.