C110-20 Pre-treatment Lung Function Scores Predict Risk of Immune Checkpoint Inhibitor-related Pneumonitis

Abstract Rationale Lung cancer is the leading cause of cancer-related mortality worldwide. The introduction of immune checkpoint inhibitors (ICIs) has improved outcomes and become standard of care. However, ICIs carry a risk of immune-related adverse events such as ICI-pneumonitis, which can impact patient outcomes and treatment continuation. We aimed to identify patients at risk for ICI-pneumonitis using the lung function score (LFS), a validated tool for prediction of pulmonary complications following stem cell transplant, which combines FEV1 and DLCO. The LFS is an additive score from 2-8 where patients are assigned more points for greater impairment in FEV1 and DLCO. Methods We retrospectively reviewed NSCLC and SCLC patients aged 21-85 years at the University of Connecticut Hospital who underwent PFTs within three years of starting ICI therapy. We excluded patients older than 80 because of limited life expectancy. ICI included PD-L1 inhibitors (Atezolizumab, Durvalumab) and PD-1 inhibitors (Pembrolizumab, Nivolumab). The primary outcome was the development of ICI-pneumonitis, defined by American College of Chest Physicians criteria: (a) compatible clinical features; (b) temporal association with ICI therapy; (c) improvement with drug cessation; (d) characteristic radiologic findings; and (e) exclusion of other cause. Demographic and clinical data were also collected. LFS were compared between Pneumonitis and Non-Pneumonitis groups, and hazard ratios (HR) with 95% confidence intervals (CI) were calculated for sequential increases in LFS and impairments in DLCO and FEV1. Results Among 1,253 patients with NSCLC or SCLC treated with immune checkpoint inhibitors, 153 had pre-treatment PFT data, of whom 41 (26.7%) developed pneumonitis. Patients with pneumonitis had lower baseline lung function across all measures: median LFS 7 4-8 vs 5 3-7 (p = 0.0098), mean FEV1 67.6 vs 75.5 % predicted (p = 0.046), and DLCO 55.2 vs 64.7 % predicted (p = 0.0067). When stratified by lung function score components, LFS 7-8 (“Severely Decreased”) was associated with a 3-fold higher risk (HR 2.90, 95 % CI 0.77-10.95) versus normal LFS 1-2. Low DLCO (≤ 60 %) conferred the greatest risk (HR 3.26, 95 % CI 1.07-9.97), followed by FEV1 ≤ 70 % (HR 1.5, 95 % CI 0.69-3.39). Conclusions Lower pre-treatment DLCO and FEV1 were strongly associated with ICI-related pneumonitis, with highest risk among patients with severely decreased LFS. Impaired baseline gas exchange and ventilatory reserve may predispose to immune-mediated lung injury. Routine PFT assessment and LFS stratification before ICI initiation may help identify patients at highest risk for ICI-pneumonitis. This abstract is funded by: None