Abstract 18841: Long-Term Cardiovascular Outcomes of Immune Checkpoint Inhibitors-Related Myocarditis: A Large Single-Center Analysis

Abstract

Introduction: Immune checkpoint inhibitors (ICI) have revolutionized the oncology landscape. Despite ICI-related cardiovascular adverse events being rare, they are often fatal in the short-term. Whether ICI-related myocarditis portends a worse long-term prognosis is unclear. Aims: To determine the long-term cardiovascular (CV) comorbidity burden and CV mortality after ICI-related myocarditis. Methods: The ICI-related adverse event registry, which includes 4195 patients who received ICI between 2011 and 2019, was screened to identify patients with ICI-related myocarditis. ICI-related myocarditis was defined according to Bonaca criteria by two independent Authors and discrepancies were further adjudicated by a staff cardiologist. Controls were randomly selected. Patients’ demographics, comorbidities, cancer history, labs, and myocarditis features on presentation were collected. Primary outcomes were freedom from CV comorbidities (a composite of atrial fibrillation, stroke, myocardial infarction, and heart failure) and freedom from CV death (CVD) at 2 years from the initiation of ICI. ICI-related myocarditis was treated as a time-varying covariate. Freedom from primary outcomes was analyzed via Kaplan-Meier analysis and Cox proportional models with backward regression were used to account for confounding. Results: A total of 76 patients developed ICI-related myocarditis at a median time of 167 days (36.8% female, mean age 69, 47% primary lung cancer). Overall, 65% and 75% of patients had EKG changes and new wall motion abnormalities, respectively. Mean LVEF was 43%, median NTproBNP was 2057, and median peak TnT was 0.81 on presentation. At 2-years follow-up, patients who developed ICI-related myocarditis had significantly lower freedom from CV comorbidities (67% vs 86.8%, p<0.001) and CVD (93.4% vs 99.3%, p=0.003). On multivariable analysis, development of ICI-related myocarditis was an independent predictor of CVD (HR 8.28, p=0.048), but not cardiovascular comorbidities (HR 2.21, p=0.08). Conclusions: This is the largest case-control study on ICI-related myocarditis demonstrating significantly worse long-term CV outcomes. Future studies are needed to optimize the management of ICI-related myocarditis survivors.