Incidence and impact of acute coronary syndrome on outcomes in chimeric antigen receptor T-cell therapy: Insights from a six-year nationwide analysis

Abstract Introduction Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of relapsed or refractory hematologic malignancies; however, it is increasingly linked to cardiovascular toxicities, particularly acute coronary syndrome (ACS). Recent evidence suggests that ACS may occur in up to 10% of CAR-T recipients, often within the first few weeks following infusion. The risk is notably heightened in the presence of severe cytokine release syndrome (CRS), a common and serious complication of CAR T-cell therapy. Despite its significant association with increased morbidity and mortality, ACS remains insufficiently studied in this setting. This study aims to assess the incidence and prognostic impact of ACS in CAR T-cell recipients using a comprehensive six-year nationwide dataset. Methods We conducted a retrospective analysis using the National Inpatient Sample (NIS) database from 2017 to 2022 to identify adult patients diagnosed with non-Hodgkin lymphoma (NHL), multiple myeloma (MM), or acute lymphoblastic leukemia (ALL) who underwent CAR T-cell therapy. Patients were stratified based on the presence or absence of ACS during hospitalization. Survey-weighted analyses were performed to generate nationally representative estimates. Multivariate logistic regression models were employed to assess the association between ACS and key clinical outcomes, adjusting for potential confounders. A two-tailed p-value of <0.05 was considered statistically significant. Results Among 5,705 adult patients who received CAR T-cell therapy, 78.7% with NHL, 15.6% with MM, and 5.7% with ALL, a total of 45 individuals (0.8%) developed ACS. Patients who developed ACS were significantly more likely to be Native American (11.1% vs. 0.4%, p < 0.05). The occurrence of ACS was independently associated with markedly higher in-hospital mortality (22.2% vs. 2.5%, p < 0.001; adjusted odds ratio [aOR], 10.0; 95% confidence interval [CI], 2.6–38.4). Additionally, ACS was associated with significantly increased risks of acute kidney injury (aOR, 5.8; 95% CI, 2.3–14.9) and respiratory failure (aOR, 6.7; 95% CI, 1.6–27.9). These patients also demonstrated a greater need for mechanical ventilation support (aOR, 23.3; 95% CI, 8.7–62.8). However, ACS was not associated with increased risk of all-cause shock or greater need for renal replacement therapy or vasopressor use. The mean length of hospital stay for CAR T-cell therapy was 16.6 days, and the mean hospitalization charge was $1,321,248.00, with no significant differences observed between the ACS and non-ACS cohorts. Conclusion In this nationwide analysis of 5,705 CAR T-cell therapy recipients from the NIS (2017–2022), the incidence of ACS was relatively low at 0.8%; however, its occurrence was associated with a tenfold increase in in-hospital mortality, as well as significantly higher risks of acute kidney injury and respiratory failure, and a greater need for mechanical ventilation. These findings underscore that, despite its infrequency, ACS confers a substantial clinical burden in this population. The results highlight the critical need for comprehensive cardiovascular risk assessment and monitoring throughout the CAR T-cell treatment continuum, particularly in patients with CRS or preexisting cardiovascular comorbidities. Future prospective studies and the implementation of standardized surveillance protocols are warranted to better identify at-risk individuals and to guide preventive and therapeutic strategies aimed at reducing ACS-related morbidity and mortality in this vulnerable cohort.