LAUSR

BACKGROUND Immune checkpoint inhibitors (ICI) are standard treatments for advanced non-small cell lung cancer and have expanded use in small cell lung cancer. While generally better tolerated than traditional chemotherapy, immune-related adverse events, such as immune checkpoint inhibitor-related pneumonitis (ICI-P), remain poorly understood toxicities that limit ICI treatment and can result in considerable morbidity. In this retrospective case-control study, we assessed a lung cancer cohort to identify ICI-P risk factors. RESEARCH QUESTION What are the risk factors, clinical presentations, radiographic findings, and outcomes for ICI-P in a real-world lung cancer cohort? Do chronic pulmonary diseases confer increased risk for ICI-P? STUDY DESIGN AND METHODS Medical records from lung cancer patients receiving nivolumab, pembrolizumab, or combination ipilimumab and nivolumab at six centers in North Carolina were reviewed (1/2004 - 7/2017). ICI-P cases and controls were characterized and logistic regression was utilized to assess for ICI-P risk factors. RESULTS 315 lung cancer patients who predominantly received nivolumab (76.5%) or pembrolizumab (22%) were included. The incidence of ICI-P was 9.5% with a median time to diagnosis of 52.5 days. The majority of ICI-P cases were high severity, and eight patients (27%) died with ongoing ICI-P treatment. Development of ICI-P was independently associated with the presence of baseline fibrosis on chest computed tomography (aOR 6.61; 95% CI 2.48 - 17.7), a composite measure of obstructive lung disease (aOR 2.79; 95% CI 1.07 - 7.29), and treatment with pembrolizumab (aOR 2.57, 95% CI 1.08 - 6.11). INTERPRETATION In this cohort, ICI-P was more common and severe than previously reported and carried an unexpectedly high mortality rate. Risk for ICI-P appears independently associated with several chronic pulmonary diseases, which may account for the higher incidence of ICI-P in lung cancer patients.