Chimeric antigen receptor T-cell therapy and cardiovascular outcomes in US Medicare beneficiaries

BACKGROUND AND AIMS: Chimeric antigen receptor T-cell (CAR-T) therapies are cellular immunotherapies that improve survival in patients with relapsed haematologic malignancies. However, their association with major adverse cardiovascular events (MACE) has received limited study, particularly in older adults. This study investigated the incidence of MACE, associated risk factors, and their impact on survival among older patients undergoing CAR-T in the USA. METHODS: Medicare fee-for-service beneficiaries over 65 who received inpatient CAR-T therapy between 2018 and 2023 were included. Baseline characteristics were assessed during the 12 months preceding CAR-T. MACE were defined as a composite of acute heart failure (HF), cardiogenic shock, myocardial infarction, cardiac tamponade, ventricular arrhythmia, complete heart block, or stroke. Multivariable models were adjusted for demographics, malignancy type, and baseline cardiovascular comorbidities. RESULTS: Among 3292 patients receiving CAR-T, 191 (5.8%) had MACE. Most common events were acute HF (3.1%), followed by ischaemic (1.3%) and haemorrhagic stroke (1%). Pre-treatment atrial fibrillation/flutter [adjusted odds ratio (aOR) 1.52 (1.08-2.16)], cardiomyopathy [aOR 2.49 (1.75-3.54)], and cerebrovascular disease [aOR 2.40 (1.30-4.43)] were independently associated with MACE. In 2021-23, MACE were also associated with immune effector cell-associated neurotoxicity syndrome and higher-grade cytokine release syndrome. MACE were associated with higher in-hospital mortality [aOR 16.9 (11.0-26.1)] and 1-year mortality after discharge [adjusted hazard ratio 1.91 (1.46-2.49)]. CONCLUSIONS: In the largest national sample of older adults receiving CAR-T, MACE occurred in 5.8% of patients and were associated with increased in-hospital and 1-year mortality. Further investigation into preventive and mitigating measures is needed.