Immune-related adverse events in older adults receiving immune checkpoint inhibitors: a comprehensive analysis of the Food and Drug Administration Adverse Event Reporting System

Abstract Background Immune checkpoint inhibitors (ICIs) have revolutionised cancer therapy, yet they carry a unique spectrum of immune-related adverse events (irAEs). Given the ageing global population and the underrepresentation of older adults in clinical trials for ICIs, we investigated the occurrence and characteristics of irAEs in older versus younger adults as well as among different age subsets within the older adult population. Methods We analysed the U.S. Food and Drug Administration Adverse Event Reporting System database reports from 2015 to 2023, focusing on ICIs. We categorised irAEs into 11 distinct types and performed descriptive and multivariate analyses to compare the prevalence and clinical characteristics of irAEs across different age groups, adjusting for potential confounding factors. Results Among 47 513 patients aged 18–100 reporting irAEs, the 65–74 and 75–84 age groups had significantly increased risks compared to 18–64 (OR 1.13, 95% CI [1.09–1.18]; 1.15 [1.1–1.21]). Cardiovascular irAEs rose with age, peaking at 75–84, while endocrine irAEs decreased. Hepatobiliary, gastrointestinal and ocular irAEs decreased with age, but renal and musculoskeletal irAEs increased, showing higher risks in older adults. Serious outcomes slightly decreased in the 85+ group, while the proportion of deaths increased with age. Conclusion We discuss the potential changes in the immune system contributing to the decreased prevalence of irAEs in the oldest age group. Additionally, conservative treatment approaches and underreporting of irAEs in older patients may influence these findings. Our findings highlight the need for personalised decision-making for ICI therapies, considering performance status and comorbidities rather than age alone.