Aims Chimeric antigen receptor T-cell therapy (CAR-T) harnesses a patient’s immune system to target cancer. There are sparse existing data characterizing death outcomes after CAR-T-related cardiotoxicity. This study examines the association between CAR-T-related severe cardiovascular events (SCE) and mortality. Methods and results From a multi-centre registry of 202 patients receiving anti-CD19 CAR-T, covariates including standard baseline cardiovascular and cancer parameters and biomarkers were collected. Severe cardiovascular events were defined as a composite of heart failure, cardiogenic shock, or myocardial infarction. Thirty-three patients experienced SCE, and 108 patients died during a median follow-up of 297 (interquartile range 104–647) days. Those that did and did not die after CAR-T were similar in age, sex, and prior anthracycline use. Those who died had higher peak interleukin (IL)-6 and ferritin levels after CAR-T infusion, and those who experienced SCE had higher peak IL-6, C-reactive protein (CRP), ferritin, and troponin levels. The day-100 and 1-year Kaplan–Meier overall mortality estimates were 18% and 43%, respectively, while the non-relapse mortality (NRM) cumulative incidence rates were 3.5% and 6.7%, respectively. In a Cox model, SCE occurrence following CAR-T was independently associated with increased overall mortality risk [hazard ratio (HR) 2.8, 95% confidence interval (CI) 1.6–4.7] after adjusting for age, cancer type and burden, anthracycline use, cytokine release syndrome grade ≥ 2, pre-existing heart failure, hypertension, and African American ancestry; SCEs were independently associated with increased NRM (HR 3.5, 95% CI 1.4–8.8) after adjusting for cancer burden. Conclusion Chimeric antigen receptor T-cell therapy recipients who experience SCE have higher overall mortality and NRM and higher peak levels of IL-6, CRP, ferritin, and troponin.

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.

Introduction: Cytokine release syndrome (CRS) and associated cardiovascular (CV) events are common following infusion of chimeric antigen receptor T cell therapy (CAR-T). There are no data characterizing whether CAR-T recipients with a pre-existing cardiac dysfunction (LVEF <53%) are at increased risk for CV events following CAR-T. Hypothesis: We hypothesized that cardiac dysfunction would be associated with a higher rate of CV events following CAR-T infusion. CV events were defined as a composite of cardiogenic shock, clinical heart failure, myocardial infarction, or arrhythmia. Methods: Patients in a multi-center registry of adult CAR-T recipients with a known baseline LVEF were included (n=241). Covariates included standard baseline CV and cancer parameters. Results: In total, 22 (9%) CAR-T patients had a pre-existing cardiac dysfunction. Those with and without [219 (91%)] baseline cardiac dysfunction were similar in age, gender, pre-existing CV risk factors, and ECOG performance status. LVEF among patients with cardiac dysfunction ranged from 25%-52%. There was no difference in prior anthracycline use, cancer type or burden, but cardiac dysfunction patients had higher rates of prior radiation (36% vs 16%, p=0.02). Cardiac dysfunction patients received less investigational CAR-T (9% vs 31%, p=0.03), more tisagenlecleucel (36% vs 18%, p=0.04), and had similar rates of axicabtagene ciloleucel and lisocabtagene maraleucel. There was no difference in mean CRS grade, rate of ≥2 grade CRS, or in tocilizumab or steroids use between those with and without cardiac dysfunction. During a median follow-up of 294 (IQR 123-661) days, 60 (25%) patients experienced CV events with more events in patients with cardiac dysfunction (63% vs 21%, p<0.001). In a Cox model adjusted for covariates identified in univariate analyses, baseline cardiac dysfunction was independently associated with an increased CV events risk (adjusted HR: 4.9, 95% CI 2.54–9.61, p<0.001) Conclusions: CAR-T recipients with pre-existing cardiac dysfunction experience more CV events despite similar rates of CRS.