Characterizing risk factors for the development of cardiovascular events in CAR-T Patients

Abstract Introduction Chimeric antigen receptor (CAR) T-cell therapy, which involves ex-vivo engineering of autologous T-cells against cancer cells, has transformed the management of B and plasma cell malignancies, leading to further efforts in identifying new targets and indications. As the use of CAR T therapy expands, understanding its effects on the cardiovascular (CV) system becomes increasingly relevant. The systemic inflammatory response elicited by CAR T therapy can result in cytokine release syndrome (CRS) with manifestations including sinus tachycardia, hypotension, arrhythmias, and in severe cases, left ventricular dysfunction and cardiogenic shock. Risk factors for CAR T related CV events are not well-described. We evaluated risk factors for a primary composite endpoint of adverse CV events in a real-world cohort of patients with B and plasma cell malignancies receiving standard of care (SOC) CAR T therapy. Methods Medical records from all consecutive patients treated with SOC CAR T cell therapy at a U.S. health system from March 2018 to December 2021 were retrospectively reviewed under an IRB approved protocol. Our outcome was a single composite endpoint of clinically significant CV events including arrhythmia, acute coronary syndrome, stroke, CV death, ejection fraction decrease under 52.5%, heart failure exacerbation, and acute pericardial disease. All events resulted in an inpatient cardiology consult, upgrade to an ICU, or outpatient cardiology appointment. A multivariable Fine-Gray model was used to model CV risk and account for the competing risk of non-CV death. Results 123 patients were evaluated with a median follow-up of 16 months. 32 (26.0%) patients experienced the composite endpoint, with 1 CV death and 18 subsequent non-CV deaths, primarily from progressive disease (PD). Of the 91 patients that did not experience an adverse CV event, 35 (28.5%) died of non-CV causes, most commonly PD. In bivariate analysis, history of Coronary Artery Disease, Atrial Fibrillation (AF), Mantle Cell lymphoma, Tyrosine Kinase Inhibitor (TKI) exposure, Eastern Cooperative Oncology Group (ECOG) score ≥ 1, and CRS grade ≥ 2 were associated with the composite outcome (Table 1). A multivariable Fine-Gray regression model developed with stepwise selection showed a history of AF, ECOG score ≥ 1, Hispanic ethnicity, or CRS grade ≥ 2 were simultaneously associated with the composite outcome (Figure 1). Conclusions Risk factors associated with adverse CV event