Incidence and characterization of myocarditis among a retrospective cohort of patients receiving immune checkpoint inhibitors
K Paik, J Hunting, A Faucheux, E Olsen, T LycanAbstract
Background/Introduction
Immune checkpoint inhibitors (ICI) are increasingly used in routine clinical practice to treat many types of cancer, leading to a growing recognition of myocarditis as a rare but potentially fatal immune-related adverse event (irAE) with a nebulous presentation.
Purpose
To estimate the incidence of ICI-associated myocarditis and identify clinical correlates of severity among real-world patients.
Methods
We created a retrospective registry of all patients who received at least one ICI dose at a comprehensive cancer center and affiliated outreach clinics (1 Feb 2011–7 Apr 2022). Trained study personnel performed structured chart reviews of routine clinical documentation to capture treatment-emergent adverse events; attribution and severity were adjudicated using National Cancer Institute definitions and criteria. Data were entered into a secure cloud-based database developed by the investigative team, validated with predefined data-quality rules, and reconciled through discrepancy resolution; clinical research specialists abstracted most records. Categorical variables were compared using Fisher’s exact test, with two-sided statistical significance set at p<0.05. The study was approved by the Institutional Review Board.
Results
Among 3,101 treated patients, 13 developed myocarditis (0.42%). Myocarditis was associated with high-grade irAEs (Common Terminology Criteria for Adverse Events Grade 3-5) more frequently than in patients without myocarditis (61.5% vs 13.7%, p<0.001). In terms of pre-treatment comorbidities, underlying thyroid comorbidity was higher in myocarditis cases (38.5% vs 17.2%, p=0.043), and cardiovascular disease trended higher (61.5% vs 36.5%, p=0.062). Age, sex, body mass index, and smoking status were not significantly different. Among patients with myocarditis, dermatologic and myositis/musculoskeletal irAEs were numerically more frequent as concurrent toxicities, though these associations did not achieve statistical significance. Unadjusted progression-free and overall survival were similar between groups.
Conclusions
ICI-associated myocarditis was rare and may have been associated with high-grade severity, thyroid comorbidity, and baseline cardiovascular disease. These data underscore the need for attentive monitoring when myocarditis is suspected and suggest a possible shared immune predisposition in patients with a history of thyroid disease. Demographic predictors were not evident. Prospective studies are needed to identify high-risk phenotypes and develop strategies for cardio-oncology surveillance and management.