Immune checkpoint inhibitor-induced myocarditis in older adults: a systematic review of associated factors

Introduction: As immune checkpoint inhibitors (ICIs) become standard treatment across an increasing range of cancers, older adults make up a growing share of recipients — yet they may also carry the highest cardiovascular risk from treatment. ICI-induced myocarditis is an uncommon but frequently fatal cardiac complication, with reported mortality of 30–50%. Older age has been repeatedly flagged as a possible risk factor, but no systematic synthesis has examined this alongside other predisposing factors. This review aimed to identify demographic, disease-related, and treatment-related factors associated with ICI-induced myocarditis, with attention to age-related risk relevant to geriatric and cardio-oncology practice.

Method: A systematic review was conducted per PRISMA 2020 guidelines. PubMed, Embase, and Cochrane were searched without date restriction. Studies reporting demographic, oncological, treatment, or long-term condition data in people who developed ICI-induced myocarditis were included. Screening and data extraction were performed independently by two reviewers, with risk of bias assessed using design-specific tools (NOS, JBI). Given clinical and methodological heterogeneity, findings were synthesised narratively.

Results: Of 1,749 records screened, 31 studies (21 controlled, 10 disease-only) met inclusion criteria. People who developed myocarditis were consistently older than controls (mean 68.1 vs 65.5 years) and more frequently male (64.7% vs 60.9%; 71.0% across disease-only studies). Combination ICI therapy was more common among cases than controls (38.4% vs 21.9%). Long-term conditions — dyslipidaemia, diabetes, and atrial fibrillation — were most consistently enriched among those affected. Thymic malignancy showed the strongest disease-related association (HR 10.9, 95% CI 2.67–44.7), alongside melanoma and renal cancer. Risk of bias was low-to-moderate among comparator-based studies but high among pharmacovigilance-derived case series.

Conclusion(s): Older age, male sex, combination immunotherapy, and specific malignancies were the factors most consistently associated with ICI-induced myocarditis. As immunotherapy use expands among older adults with long-term cardiovascular conditions, these findings support closer cardiac monitoring for those at higher risk — an emerging area of overlap between geriatric medicine and cardio-oncology. Standardised diagnostic criteria and age-stratified data are needed in future prospective research.