Survival Outcomes After Immune-Related Adverse Events in Older Adults With Advanced Non–Small Cell Lung Cancer

BACKGROUND: Immune-related adverse events (irAEs) are common toxicities of immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC), but their prognostic implications in older adults remain uncertain. PATIENTS AND METHODS: We conducted a retrospective cohort study using SEER-Medicare (2010-2019). We included patients aged ≥66 years with locally advanced or metastatic NSCLC who initiated ICI monotherapy or chemoimmunotherapy from 2015-2017. Follow-up began at treatment initiation and continued until death, Medicare disenrollment, or December 31, 2019. The primary exposure was a clinically meaningful irAE, defined as an irAE diagnosis with evidence of systemic immunosuppressant use and/or treatment delay, or discontinuation. In secondary analyses, we categorized patients as having no irAE, an irAE managed without hospitalization, or an irAE requiring hospitalization. The primary outcome was overall survival. We estimated adjusted survival differences and restricted mean survival time using doubly robust causal inference methods. RESULTS: The cohort included 5,304 patients (mean age, 75 years; 52.7% female; 81.9% White). Clinically meaningful irAEs occurred in 1,807 (34.1%) patients, with a median onset of 3.8 months (IQR, 1.1-9.4). Death occurred in 65.1% of patients with irAEs and 78.7% without irAEs, corresponding to an adjusted absolute survival benefit of 6.6% (95% CI, 5.3%-8.0%) and a 6.5-month gain in restricted mean survival time (95% CI, 5.6-7.4). In secondary analyses, irAEs managed without hospitalization showed the greatest benefit (odds ratio [OR], 0.44; 95% CI, 0.35-0.54), whereas irAE hospitalization was associated with attenuated benefit (OR, 0.94; 95% CI, 0.89-0.99). CONCLUSIONS: Among older adults with advanced NSCLC receiving ICIs, clinically meaningful irAEs were associated with improved overall survival, particularly when managed without hospitalization. These findings highlight the clinical importance of early recognition of immune-related toxicities; irAE-related hospitalization may identify a higher-risk group warranting closer monitoring and supportive care.