Characterization of Cardiovascular Events and Prognosis in Immune Checkpoint Inhibitor-Related Myocarditis.

Abstract

Objective: To evaluate the incidence, timing, and characteristics of immune checkpoint inhibitor-related myocarditis (ICIrM) and associated cardiovascular events at 3-year follow-up.

Methods: All patients treated with immune checkpoint inhibitors (ICIs) at a multicenter institution from 2011 to 2022 were retrospectively reviewed for ICIrM. A propensity score-matched control group was identified from patients treated with ICIs without development of myocarditis (ratio of 1:4). Baseline characteristics, cardiovascular events, and mortality outcomes were manually curated during extended 3-year follow-up. Major adverse cardiovascular events (MACE) were defined as transient ischemic attack/stroke, heart failure, and myocardial infarction.

Results: Of 5423 patients treated with ICIs, ICIrM occurred in 59 (1.1%), and 236 propensity score-matched patients who received ICIs without myocarditis were identified as controls. Mean age was 68.5 ± 12.3 years; 65.4% were male. Median time to development of ICIrM was 44 days (interquartile range, 28 to 102 days), with median troponin value of 364 ng/L (interquartile range, 115 to 1224 ng/L). Patients with ICIrM had increased risk of cardiac death (hazard ratio [HR], 34.0; 95% CI, 7.8 to 148.0; P<.001), MACE (HR, 5.0; 95% CI, 3.1 to 8.1; P<.001), ventricular tachycardia (HR, 12.3; 95% CI, 1.3 to 118.4; P=.03), and complete heart block (HR, 2.3; 95% CI, 1.0 to 5.1; P=.046); these occurred predominantly within 120 days after diagnosis of ICIrM. Triple-M syndrome (myocarditis, myasthenia, and myositis) occurred in 12 (20.3%), with increased risk for all-cause mortality (HR, 2.1; 95% CI, 1.0 to 4.1; P=.04) but not for cardiac death or MACE.

Conclusion: Immune checkpoint inhibitor-related myocarditis is associated with increased cardiovascular events that are further characterized on extended follow-up, with most occurring in the first 4 months after diagnosis.