Immune Checkpoint Inhibitor-Associated Myocarditis: A Retrospective Case Series.

Abstract

Background: Immune checkpoint inhibitors (ICIs) improve outcomes across malignancies but can cause immune-related adverse events (irAEs), notably myocarditis, with case-fatality up to 50%.

Methods: We retrospectively reviewed five patients with potential ICI-associated myocarditis treated at Mayo Clinic Florida (2019-2024) and summarize the existing literature. Cases were retrospectively categorized as definite, probable, or possible myocarditis according to cardiac magnetic resonance (CMR) findings and histopathology when available.

Results: The median age was 74 years, and four of the five patients were male. Myocarditis developed between 5 and 30 days after initiation of anti-PD-1 therapy. Presentations included dyspnea (three patients), chest pain (one patient), and asymptomatic troponin elevation detected on routine monitoring (one patient). Troponin T elevation above the 99th percentile was seen in all five cases (normal <15 ng/L). Electrocardiograms (ECG) demonstrated conduction abnormalities or ventricular ectopy in each patient. Left ventricular ejection fraction was preserved in four patients and severely reduced in one. CMR provided findings supportive of myocarditis in two of the five cases, while one endomyocardial biopsy (EMB) was performed and did not demonstrate active inflammation. Based on predefined criteria, one case was classified as definite myocarditis, one as probable, and three as possible ICI-associated myocarditis. All five patients received corticosteroid therapy. Two required escalation of immunosuppression. One patient developed concurrent myasthenia gravis, consistent with myocarditis-myositis-myasthenia (MMM) overlap, and underwent plasmapheresis for the neuromuscular component. Three patients recovered. Two patients died during follow-up; in both cases, myocarditis was considered a contributing factor, although direct causality could not be definitively established.