Age-stratified reporting of immune checkpoint inhibitor-associated myocarditis: disproportionality is amplified in older adults, with implications for geriatric oncology
- 1Department of Internal Medicine, Division of Geriatrics, Hacettepe University Faculty of Medicine
Abstract
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.
Related
- Integrated multi-omics identifies distinct immune signatures with diagnostic and therapeutic implications in immune checkpoint inhibitor-induced myocarditis
- A serum proteomics‐based predictive model for steroid‐resistant immune checkpoint inhibitor associated myocarditis
- Age-stratified signals and early onset of adverse events with pregabalin: a disproportionality analysis of the FDA adverse event reporting system
- Rechallenge After Immune Checkpoint Inhibitors Myocarditis: Evidence and a Practical Framework
- Research advances in Janus kinase inhibitors for immune checkpoint inhibitors-related myocarditis
BibTeX
@article{pehlivan2026agestratified,
title = {{Age-stratified reporting of immune checkpoint inhibitor-associated myocarditis: disproportionality is amplified in older adults, with implications for geriatric oncology}},
author = {Murat Pehlivan and Aybüke Uyar and Okan Turhan and Özge Özgün and Oğuz Kayabaşı and Arzu Okyar Baş and Cafer Balcı and Burcu Balam Doğu and Meltem Gülhan Halil and Mustafa Cankurtaran and Mert Eşme},
journal = {Frontiers in Cardiovascular Medicine},
year = {2026},
month = oct,
doi = {10.3389/fcvm.2026.1948161},
url = {https://www.frontiersin.org/articles/10.3389/fcvm.2026.1948161/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Age-stratified reporting of immune checkpoint inhibitor-associated myocarditis: disproportionality is amplified in older adults, with implications for geriatric oncology
AU - Murat Pehlivan
AU - Aybüke Uyar
AU - Okan Turhan
AU - Özge Özgün
AU - Oğuz Kayabaşı
AU - Arzu Okyar Baş
AU - Cafer Balcı
AU - Burcu Balam Doğu
AU - Meltem Gülhan Halil
AU - Mustafa Cankurtaran
AU - Mert Eşme
PY - 2026
DA - 2026/10/13
JO - Frontiers in Cardiovascular Medicine
DO - 10.3389/fcvm.2026.1948161
UR - https://www.frontiersin.org/articles/10.3389/fcvm.2026.1948161/full
AB - 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.
SN - 2297-055X
ER -