Background: Chimeric antigen receptor (CAR) T-cell therapy has evolved as a viable treatment option for selected patients with advanced B-cell lymphomas and leukemias. However, the use of CAR T-cells may be limited by severe toxicities and organ dysfunction. While the cytokine release syndrome, a systemic inflammatory response, is a well-recognized complication, data on cardiovascular toxicity in the context of CAR T-cell therapy are still scarce. The objective of this analysis was to investigate the cardiovascular complications and outcomes in patients undergoing CAR T-cell treatment in a single-center study.

Methods: A total of 62 patients receiving CAR T-cell therapy were enrolled in an observational database. Clinical data including cardiovascular biomarkers were obtained. Cancer therapy-related cardiovascular toxicity (CTR-CVT) was defined as a composite of new cancer therapy-related cardiac dysfunction (CRTCD), arrhythmia, cardiogenic shock, myocardial infarction and cardiovascular death. Median follow-up was 305 days.

Results: CTR-CVT occurred in 58.1% of all patients and was predominantly caused by mild-moderate forms of CTRCD (54.8%) and new-onset of atrial fibrillation (14.5%). Severe CTRCD was observed in two patients (3.2%). No cases of myocardial infarction, cardiogenic shock or cardiovascular death were noted. Patients with CTR-CVT were significantly older (median 67.7 years vs. 57.9 years, p=0.012) and had higher baseline levels of NT-proBNP (median 314 pg/ml vs. 72 pg/ml, p=0.003), high-sensitivity Troponin T (median 18 pg/ml vs. 10 pg/ml, p=0.005) and C-reactive protein (median 28 mg/l vs. 7 mg/l, p=0.001) compared to patients without CTR-CVT. Receiver operating characteristic curve analysis showed a good degree of separability for baseline NT-proBNP (0.73, 95% CI 0.59-0.86, p=0.003), high-sensitivity Troponin T (AUC 0.72, 95% CI 0.58-0.86, p=0.006) and C-reactive protein (0.74, 95% CI 0.60-0.87, p=0.002) regarding CTR-CVT. After a median follow-up of 305 days, CTR-CVT was not significantly associated with all-cause mortality (p = 0.823, log-rank test).

Conclusions: CTR-CVT including new-onset arrhythmia, is a frequent complication during CAR T-cell therapy. Baseline biomarkers such as NT-proBNP, high-sensitivity Troponin T and C-reactive protein may be useful for improved cardiovascular risk stratification. Future studies are needed to optimize treatment algorithms and to investigate the long-term prognostic implications of CTR-CVT in CAR T-cell therapy recipients.