Impact of age on immune-related toxicities and survival in non–small cell lung cancer treated with immune checkpoint inhibitors: A multicenter retrospective study.

Abstract

e20641 Background: Immune checkpoint inhibitors (ICIs) are a cornerstone of therapy for non-small cell lung cancer (NSCLC). They can cause immune-related adverse events (irAEs), which may vary with age due to immunosenescence, inflammaging, and comorbidity burden. Older adults are underrepresented in clinical trials, limiting real-world data on age-related toxicity. We evaluated differences in irAEs and overall survival (OS) between younger and older NSCLC patients treated with ICIs. Methods: We conducted a multicenter retrospective cohort study using the TriNetX federated electronic medical record network (113 healthcare organizations). Adults with NSCLC who received ICIs between January 2010 and January 2026 were included. Cohort 1 comprised patients aged 18–64 years; cohort 2 had patients aged 65–90 years. Patients with systemic lupus erythematosus were excluded. The index event was initiation of immunotherapy. ICIs included pembrolizumab, nivolumab, atezolizumab, durvalumab, and ipilimumab. Cohorts were propensity score-matched 1:1 for over 30 variables, including sex, race, major comorbidities, and immunotherapy type. After matching, 1,422 patients were included in each cohort. Outcomes included irAEs (diarrhea, rash, autoimmune thyroiditis, pneumonitis, and adrenalitis) and OS. Autoimmune hepatitis and hypophysitis were excluded due to fewer than 10 events in both cohorts. Odds ratios were calculated for irAEs, and OS was evaluated using Kaplan-Meier analysis with log-rank testing. Results: After propensity matching, baseline characteristics and immunotherapy exposure were balanced between cohorts. Pembrolizumab was most frequently used (59.4% vs 56.6%), followed by nivolumab (20.6% vs 24.0%), atezolizumab (7.5% vs 5.2%), durvalumab (12.3% vs 14.0%), and ipilimumab (4.1% vs 3.9%) in younger and older cohorts, respectively. Younger patients had a significantly higher incidence of rash compared to older patients (212 vs 147, p < 0.001), while rates of autoimmune thyroiditis, pneumonitis, adrenalitis, and diarrhea were similar (p > 0.05). Kaplan-Meier analysis showed a significant difference in OS between cohorts (891 days vs 731 days, p = 0.011). Conclusions: This real-world analysis shows that ICIs have a similar overall toxicity profile across age groups in NSCLC. Rates of most irAEs were comparable between younger and older adults after propensity matching. The higher incidence of rash in younger patients may reflect stronger immune activation and could serve as a marker of enhanced response to immunotherapy. Our results show that increased age alone does not lead to worse toxicity; future studies are needed to define optimal patient selection.