Abstract 10135: Cardiotoxicity and Mortality in Chimeric Antigen Receptor T Cell Therapy Recipients

Abstract

Introduction: Chimeric antigen receptor T cell (CAR-T) therapy harnesses a patient’s own immune system to target cancer. Cardiotoxicity occurs in up to 25% of patients treated with CAR-T. There are limited data characterizing the association between the development of cardiotoxicity after CAR-T and mortality among patients following CAR T cell therapy. Hypothesis: We hypothesized that cardiotoxicity following CAR-T treatment would be associated with a higher rate of mortality. Cardiotoxicity was a composite outcome defined as the development of heart failure, cardiogenic shock, or myocardial infarction. Methods: We included the first 202 adult patients entered into a multicenter registry receiving anti-CD 19 CAR-T for lymphoma or acute lymphoblastic leukemia (ALL). Of these, 108 died and 94 survived. Covariates included standard baseline cardiovascular and cancer parameters, the occurrence of cardiotoxicity and mortality. Results: Those that did and did not die after CAR-T were similar in age, sex, and pre-lymphodepletion chemotherapy regiment. Death after CAR-T was more common in patients with than without hypertension (66% vs. 47%, p=0.009) or ALL (66% vs. 48%, p=0.02), and less common with baseline coronary artery disease (25 vs. 56%, p=0.04). There was no difference in mean cytokine release syndrome (CRS) grade, rate of ≥2 CRS, or in the use of tocilizumab or steroids between those who did and did not die after CAR-T. During a mean follow-up of 372±284 days, 33 (16%) patients experienced cardiotoxicity. Patients with vs. without cardiotoxicity died more often (76% vs. 49%, OR 3.2, CI 1.4 - 7.6, p=0.005). In a Cox model adjusted for covariates identified in univariate analyses, occurrence of cardiotoxicity with CAR-T was independently associated with an increased risk of mortality (adjusted HR: 1.85, 95% CI: 1.17-2.92, p=0.009). Conclusions: CAR-T recipients who experience cardiotoxicity have higher mortality.

Cardio-Oncology: A New Discipline in Medicine and Its Relevance to Hematology

“…The incidence of cardiac events in patients receiving CAR-T cells varies between studies but is generally between 10 and 20% and occurs mainly in CRS grade ≥2 with elevated cardiac troponin and interleukin-6. 67 68 69 70 71 72 73 The most frequently observed CV events are profound hypotension requiring vasopressor support, arrhythmias including AF and ventricular tachycardias, as well as left ventricular dysfunction, decompensated HF, and CV death. 67 68 69 70 71 72 73…”

“…67 68 69 70 71 72 73 The most frequently observed CV events are profound hypotension requiring vasopressor support, arrhythmias including AF and ventricular tachycardias, as well as left ventricular dysfunction, decompensated HF, and CV death. 67 68 69 70 71 72 73…”

Biomarkers and cardiovascular outcomes in chimeric antigen receptor T-cell therapy recipients

“…[6][7][8] Recent studies have shown that cardiovascular (CV) events after CAR-T can occur in up to one in four-five patients, including cardiomyopathy (10%), clinical heart failure (6%), and myocardial infarction (MI) (5%). [9][10][11][12][13][14] However, it is unknown whether the occurrence of a CV event impacts mortality in patients undergoing CAR-T. Understanding the association between CV events and mortality is important to further advance CV monitoring guidelines in CAR-T recipients. 15 Similarly, prevention and early treatment of cardiotoxicity may further improve survival outcomes in this population.…”