Differential Toxicity of Immune Checkpoint Inhibitors in Older Adults: A Large-Scale, Propensity Score-Matched Real-World Analysis

BACKGROUND: The risk-benefit profile of immune checkpoint inhibitors (ICIs) in the understudied elderly population (≥75 years) remains poorly defined. We characterized clinical outcomes and immune-related adverse events (irAEs) in this population using a large real-world dataset. METHODS: Using the TriNetX network, we identified cancer patients initiating ICIs, creating two cohorts: ≥75 and 18-74 years. After 1:1 propensity score matching (PSM), we compared overall survival, all-cause hospitalization, and 5-year irAE risk. RESULTS: We matched 37,417 older patients to 37,417 younger controls. Older adults had worse overall survival (median 753 vs 955 days; HR 1.15; 95% CI 1.13 - 1.18). Paradoxically, they had lower risks for endocrine (RR 0.86; 95% CI 0.83 - 0.89) and gastrointestinal (RR 0.80; 95% CI 0.76 - 0.84) events. However, risks significantly increased for myocarditis (RR 1.27; 95% CI 1.05 - 1.53), myasthenia gravis (RR 2.38; 95% CI 1.76 - 3.21), polymyalgia rheumatica (RR 2.12; 95% CI 1.62 - 2.76), pemphigoid (RR 2.05; 95% CI 1.58 - 2.67), and acute kidney injury (RR 1.09; 95% CI 1.05 - 1.13). CONCLUSION: Patients ≥75 years exhibited poorer survival and a unique irAE profile characterized by lower overall incidence but heightened risk of specific, highly morbid toxicities. These findings highlights the need for age-specific vigilance in geriatric oncology.