Chimeric antigen receptor T-cell (CAR-T) therapies have improved survival for relapsed haematologic malignancies, but their cardiovascular safety profile among older adults has been incompletely characterised. This study analysed the incidence of major adverse cardiovascular events (MACE), associated baseline risk factors, and the relationship between MACE and survival among US Medicare beneficiaries aged over 65 who underwent inpatient CAR-T therapy between 2018 and 2023.
The investigators identified Medicare fee-for-service beneficiaries older than 65 who received inpatient CAR-T therapy from 2018 through 2023. Baseline patient characteristics and comorbidities were assessed using data from the 12 months preceding CAR-T administration. The primary cardiovascular outcome was a composite MACE endpoint defined to include: acute heart failure, cardiogenic shock, myocardial infarction, cardiac tamponade, ventricular arrhythmia, complete heart block, or stroke.
Multivariable models adjusted for demographics, type of malignancy, and baseline cardiovascular comorbidities were used to evaluate factors associated with MACE. For later years (2021–2023), the analysis also evaluated associations between MACE and immune-related complications documented in claims, specifically immune effector cell-associated neurotoxicity syndrome and higher-grade cytokine release syndrome. Mortality outcomes included in-hospital death and 1-year mortality after discharge; adjusted effect estimates were reported.
A total of 3,292 Medicare beneficiaries received inpatient CAR-T during the study window. Of these, 191 patients (5.8%) experienced MACE during the index hospitalization.
The most common individual cardiovascular event was acute heart failure, which occurred in 3.1% of patients. Cerebrovascular events were also present: ischaemic stroke occurred in 1.3% of patients and haemorrhagic stroke in 1.0%.
Pre-treatment cardiovascular conditions that were independently associated with MACE included atrial fibrillation/flutter (adjusted odds ratio [aOR] 1.52; 95% CI 1.08–2.16), cardiomyopathy (aOR 2.49; 95% CI 1.75–3.54), and cerebrovascular disease (aOR 2.40; 95% CI 1.30–4.43).
In the subgroup covering 2021–2023, MACE were additionally associated with immune-related toxicities captured in claims data, specifically immune effector cell-associated neurotoxicity syndrome and higher-grade cytokine release syndrome.
Occurrence of MACE was strongly linked to mortality. Patients with MACE had significantly higher odds of in-hospital death (aOR 16.9; 95% CI 11.0–26.1). Among patients who survived to discharge, MACE were associated with an increased risk of death within 1 year after discharge (adjusted hazard ratio 1.91; 95% CI 1.46–2.49).
In this large national sample of older adults receiving CAR-T therapy, MACE occurred in 5.8% of patients and were predominantly driven by acute heart failure and stroke. Pre-existing arrhythmia, cardiomyopathy, and prior cerebrovascular disease were independent predictors of MACE. The linkage of MACE to immune toxicities in 2021–2023 suggests interactions between treatment-related inflammatory syndromes and cardiovascular complications.
Most importantly, MACE were associated with markedly worse short-term and longer-term survival, with a large increase in adjusted in-hospital mortality and nearly double the hazard of 1-year post-discharge mortality.
These findings highlight the need for heightened cardiovascular assessment and risk stratification in older adults considered for CAR-T therapy. Attention to pre-existing conditions such as atrial fibrillation/flutter and cardiomyopathy, and to cerebrovascular disease, may help identify patients at higher risk for MACE.
The observed association between MACE and immune toxicities (higher-grade cytokine release syndrome and neurotoxicity) underscores the potential value of integrated cardio-oncology care pathways during CAR-T administration, and suggests that strategies to prevent or mitigate severe immune-related adverse events may also reduce cardiovascular complications.
Further investigation is needed into targeted preventive measures, monitoring protocols, and treatment modifications to reduce MACE incidence and improve survival in this population.
The abstract reports findings derived from Medicare fee-for-service claims and adjusted multivariable models, but does not provide detailed information on center-specific practices, the specific CAR-T products used, or granular timing and management of cardiovascular events beyond what is summarized. Readers interested in full methods, additional subgroup analyses, or figure-level data are referred to the full text (PMCID: PMC13380970; DOI: 10.1093/eurheartj/ehag394) for complete details.