Cardiovascular effects of chimeric antigen receptor t-cell therapy for refractory or relapsed non-hodgkin lymphoma

Abstract

Abstract Purpose Cardiovascular complications of chimeric antigen receptor T-cell (CAR T-cell) therapy are poorly understood. We examined the incidence, predictors and impact of new or worsening cardiomyopathy in patients undergoing CAR T-cell therapy. Methods All patients with refractory or relapsed non-Hodgkin's lymphoma, undergoing CAR T-cell therapy at collaborative institutes underwent serial echocardiograms at baseline and within 7 days after developing high-grade cytokine release syndrome (CRS), and were followed for all-cause mortality. New or worsening cardiomyopathy was defined as a reduction in left ventricular ejection fraction (LVEF) >10% from baseline to <50% during the index hospitalization. Results Among 187 consecutive CAR T-cell therapy patients, 116 (50 Grade ≤1 CRS, 66 Grade ≥2 CRS) had >1 echocardiogram performed and were included in this analysis. The median age was 63 (range 19–80) years, 42% were women, 91% were Caucasian. A total of 12 (10.3%) patients developed new or worsening cardiomyopathy with a decline in LVEF from 58±6% to 36±7% within a median of 12.5 (range 2–24) days of CAR T-cell infusion. In multivariable analyses, older age, prior stem cell transplantation, baseline angiotensin-converting enzyme inhibitor use and CRS grade ≥2 were associated with the development of cardiomyopathy. Patients who developed cardiomyopathy were more likely to require vasopressor support (p=0.004) and mechanical ventilation (p=0.014). LVEF improved in 9/12 (75%) patients. CAR T-cell associated cardiomyopathy did not impact overall mortality or cancer response to CAR-T cell therapy. Conclusions Patients undergoing CAR T-cell therapy are at risk of developing cardiomyopathy and hemodynamic instability. Pre-CAR T-cell therapy cardiovascular risk stratification and echocardiogram surveillance during therapy should be considered for prompt identification and mitigation of cardiac complications. Predictors of Cardiomyopathy Development Funding Acknowledgement Type of funding source: Private hospital(s). Main funding source(s): Anju Nohria, MD is supported by the Gelb Master Clinician Award at Brigham and Women's Hospital.