Inhaled corticosteroid use and risk of pneumonitis in patients treated with immune checkpoint inhibitors.
3140 Background: The identification of risk factors for immune-related adverse events (irAEs) is an important area of research. Among irAEs, pneumonitis carries one of the highest morbidities. There is a lack of strong predictors for pneumonitis in patients (pts) treated with ICI. We sought to identify predictors for the development of pneumonitis, and whether the use of inhaled corticosteroids (ICS) at time of ICI could be protective. Methods: Pts with advanced cancer treated with ICI from 2011 and 2018 were included in this retrospective study. Pneumonitis attribution to ICI was determined by treating physician at time of diagnosis. Time to pneumonitis was defined as days from the start of ICI to pneumonitis diagnosis. Pts who never had pneumonitis were censored at the time of last follow up or death. Predictors of pneumonitis were assessed by univariate Cox proportional hazard models at a significance threshold of alpha = 0.05. Results: A total of 837 pts were identified, and 30 (3.6%) pts developed any grade pneumonitis (12 grade 2, 14 grade 3, 1 grade 4, 3 grade 5) after receiving ICI (Table). Pts with age ≥65 years (y) had increased risk of developing pneumonitis over pts with age < 65y (HR 2.1, 95 CI: 1.02-4.4, p=0.041). 82 (9.7%) of the total cohort were on inhaled corticosteroid (ICS) at time of ICI, and 9 (11%) developed pneumonitis. Rather than being protective, pts on ICS had higher risk of pneumonitis (HR 4.2, 95 CI: 1.9-9.2, p=0.001). Pts with lung cancer had an increased risk for pneumonitis compared to pts with other cancers (HR 3.2, 95 CI: 1.5-6.4, p =0.003). Other risk factors included performance status, smoking history, line of therapy, or prior treatment including radiation were not statistically significant. Conclusions: Rather than a protective effect of ICS, our analysis found a higher risk of pneumonitis in pts treated with ICS. We confirmed an increased risk of pneumonitis for lung cancer pts compared to pts with other cancers, and higher risk of pneumonitis in pts age >65y. We hypothesize that the increased inflammatory status in chronic lung inflammation may predispose pts to pneumonitis that was not ameliorated by ICS. Future study is needed in prospective cohorts to further clarify the underlying inflammatory mechanism. [Table: see text]