Immune checkpoint inhibitor–associated myocarditis: Incidence, risk factors, and clinical outcomes in a global real-world cohort.

11177 Background: Immune checkpoint inhibitor (ICI)-associated myocarditis is a rare but life-threatening immune-related adverse event (irAE), with a mortality rate of 30–50%. Most available evidence comes from case series and adverse event reporting databases, leaving its risk factors and clinical outcomes largely undefined. Methods: We performed a retrospective investigation using the TriNetX Global Research Network. Patients were included if they had been diagnosed with solid tumors after 2016 for which ICIs are approved. We calculated myocarditis incidence among ICI users and compared myocarditis risk between ICI and non-ICI cohorts using propensity score matching (accounting for demographics, comorbidities, cancer types, and treatments). Univariate and multivariate models were applied to assess risk factors. Risks of hospitalization, ICU admission, and major adverse cardiovascular events (MACE) were compared in ICI-treated patients with and without myocarditis using propensity score matching. Results: Among 130,234 ICI-treated patients, 643 (0.49%) developed myocarditis. Most cases (82.0%) occurred within the first year of ICI initiation. The risk of myocarditis was 27 times higher in the ICI group compared to the non-ICI group (Relative Risk [RR]=27.78, 95% CI: [17.36-44.45]). Univariate analysis identified older age, male sex, White race, hypertension, hyperlipidemia, ischemic heart disease, diabetes, chronic kidney disease, heart failure, cardiomyopathy, urothelial cancer, melanoma, ipilimumab, nivolumab, pembrolizumab, radiation therapy, inflammatory arthritis, lupus, and systemic connective tissue disease as potential risk factors. In multivariate analysis, only age over 65 (Hazard Ratio [HR] = 1.34, 95% CI: [1.11–1.63], p < 0.01), hypertension (HR=1.31, 95% CI: [1.06-1.62], p=0.01), hyperlipidemia (HR=1.34, 95% CI: [1.09-1.65], p<0.01), melanoma (HR=1.52, 95% CI: [1.25-1.86], p<0.01), and ipilimumab (HR= 2.44, 95% CI: [1.87-3.19], p<0.01) were significantly associated with myocarditis. Patients who developed ICI-associated myocarditis had higher risks of hospitalization (RR=1.39, 95% CI: [1.28-1.52]), ICU admission (RR=2.35, 95% CI: [1.86-2.98]), myocardial infarction (RR=5.58, 95% CI: [3.73-8.34]), heart failure (RR=1.59, 95% CI: [1.38-1.85]), stroke (RR=2.94, 95% CI: [1.75-4.97]), MACE (RR=3.92, 95% CI: [2.91-5.27]), and all-cause mortality (RR=1.32, 95% CI: [1.13-1.55]) within one year compared to those who received ICIs but did not develop myocarditis. Conclusions: ICI-associated myocarditis is a rare irAE but carries an increased risk of cardiovascular complications and death. Advanced age, hypertension, hyperlipidemia, melanoma, and ipilimumab use appear to be risk factors. Clinical vigilance is warranted to facilitate early detection and management of this potentially fatal complication.