Age-stratified reporting of immune checkpoint inhibitor-associated myocarditis: disproportionality is amplified in older adults, with implications for geriatric oncology
Background Cardiovascular toxicity is the immune-related adverse event with the highest reported fatality proportion among immune checkpoint inhibitor (ICI) complications; myocarditis mortality reaches 50%. ICI use has expanded into older populations underrepresented in pivotal trials, but cardiotoxicity reporting in these patients has not been quantified. Methods ICI-associated cardiac adverse event records submitted to the FDA Adverse Event Reporting System (FAERS) between January 2011 and March 2026 were retrieved via openFDA. Six ICI agents (pembrolizumab, nivolumab, ipilimumab, atezolizumab, durvalumab, cemiplimab) were crossed with 18 MedDRA Preferred Terms across six cardiac event categories; myocarditis terms were combined at the unique-report level. Reporting odds ratios (RORs) for myocarditis were calculated against the full FAERS background and stratified by age (<65 vs. ≥65 years). RORs reflect reporting disproportionality and do not represent true clinical incidence. Results We identified 4,107 unique ICI-associated myocarditis reports and 18,261 cardiac AE records. Among 3,996 age-recorded myocarditis reports, 63.4% occurred in patients aged ≥65 and 28.3% in ≥75 — far exceeding pivotal-trial participation of these age groups. The pooled myocarditis ROR was 34.21 (95% CI 32.95–35.51); agent-specific RORs ranged from 18.73 (atezolizumab) to 41.99 (cemiplimab). Reporting odds for myocarditis were higher in patients aged ≥65 than in those aged <65 for every agent examined; among the five agents with adequate numbers in both strata the amplification ranged from 1.6- to 3.1-fold. Cemiplimab, whose 51 myocarditis reports include 30 with a recorded age and only 3 in the <65 comparison stratum, returned the largest values on every age-related metric; on denominators of that size these are not stable estimates and are reported in the main text rather than here. Conclusions ICI-associated myocarditis reporting is disproportionately concentrated in older adults, and the disproportionality signal is amplified in this group across all six agents. The class-wide age effect, rather than the estimate for any single agent, is the principal finding. Older adults appear disadvantaged on two fronts: under-representation in the pivotal trials that established ICI safety profiles, and an age-amplified pharmacovigilance signal. Integrating pre-ICI cardiac evaluation into geriatric oncology practice is a priority as ICI use expands further into older populations.
Authors
- Murat Pehlivan (ORCID: https://orcid.org/0000-0001-5427-2122)
- Burcu Balam Doğu (ORCID: https://orcid.org/0000-0002-4430-6146)
- Meltem Gulhan Halil (ORCID: https://orcid.org/0000-0001-7597-8140)
- Okan Turhan (ORCID: https://orcid.org/0000-0002-9334-4122)
- Mustafa Cankurtaran (ORCID: https://orcid.org/0000-0002-8213-7515)
- Aybüke Uyar (ORCID: https://orcid.org/0009-0003-3610-5752)
- Özge Özgün (ORCID: https://orcid.org/0000-0002-0104-6604)
- Cafer Balcı
- Oğuz Kayabaşı
- Arzu Okyar Baş
- Mert Eşme
Institutions
- Hacettepe University (TR)
Publication Details
- Journal
- Frontiers in Cardiovascular Medicine
- Published
- 2026-10-13
- DOI
- https://doi.org/10.3389/fcvm.2026.1948161
- Primary Topic
- Pharmacovigilance and Adverse Drug Reactions
- Type
- article
- Field-Weighted Citation Impact
- 0.00