Immune-related adverse events and patient outcomes in non–small cell lung cancer: A silver lining?

e20060 Background: Immune checkpoint inhibitor (ICI) therapy has prolonged survival in non-small cell lung cancer (NSCLC), but can also trigger immune-related adverse events (irAEs) requiring therapy discontinuation and re-challenge. Data on morbidity and response outcomes after irAEs, as well as tolerability of re-challenge after irAE, remains limited in these patients. Methods: We conducted a retrospective, single-institution analysis of patients with primary lung malignancy who received immunotherapy at the University of Virginia Emily Couric Cancer Center between 2011-2023. Data on treatment patterns, demographics, survival outcomes, irAEs, and rechallenge after irAE were collected. IrAEs were graded using CTCAE v5. criteria via chart review. Median overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method. Hazard ratios (HR) were from multivariable Cox regression models, and associated p-values were calculated from Wald tests. Results: Of 598 NSCLC patients who received ICI, 55.7% were male, 81.8% were White, and median age was 65 years. 61.7% had Stage IV disease at diagnosis, and 57.0% of patients had adenocarcinoma on histology. 282 (47.2%) patients experienced an irAE. The most common irAEs experienced were rash (24.8%), pneumonitis (22.7%), and hypothyroidism (11.0%). Of patients who experienced an irAE, 194 (68.8%) underwent ICI re-challenge. Of patients who underwent re-challenge, 59 (30.3%) experienced a subsequent irAE. OS for the whole cohort was 29.1 months (95% CI: 24.8-33.9 months) and PFS was 6.9 months (95% CI: 6.4-8.2 months). Having squamous cell carcinoma histology was associated with decreased OS (HR = 1.47, p = 0.002) compared to adenocarcinoma, as was stage IV disease at diagnosis (HR = 1.83, p = 0.001) vs. stage I. Patients who experienced an irAE had improved OS (HR = 0.55, p < 0.001) and PFS (HR = 0.46, p < 0.001) compared to patients who did not experience one. Conclusions: Occurrence of irAE was associated with improved OS and PFS in NSCLC patients. Additionally, ICI re-challenge is feasible in most patients after irAE. Further studies are needed to evaluate factors associated with successful ICI re-challenge.