Influence of inhaled corticosteroids on immune checkpoint inhibitor pneumonitis and mortality in patients with COPD and lung cancer.

Abstract

e20628 Background: The use of inhaled corticosteroids (ICS) in patients with chronic obstructive pulmonary disease (COPD) requires careful clinical judgment to balance factors such as disease severity, exacerbation frequency, and peripheral eosinophil counts with the risk of infection. In lung cancer, immune checkpoint inhibitors (ICIs) utilize the host immune system to detect and eliminate malignant cells. However, ICS are inherently immunosuppressive, which raises concerns about their interactions with ICI therapy. The role of ICS specifically in the management of COPD among lung cancer patients receiving ICIs remains underexplored. Methods: The TriNetX global federated research network was utilized to identify real-world cohorts of patients with COPD treated with long-acting beta agonists (LABA) and long-acting muscarinic antagonists (LAMA), with or without ICS, who subsequently developed lung cancer and were treated with an ICI. Patients treated with ICS were compared to a 1:1 propensity score-matched (PSM) cohort of patients not treated with ICS to reduce confounding. Primary outcomes included one-year mortality and the development of ICI pneumonitis within one-year following lung cancer diagnosis and initiation of an ICI. The secondary outcome was the risk of infection. Relative risks (RR) were calculated to assess associations between ICS use and ICI pneumonitis or infection, while Kaplan-Meier analysis was used to determine mortality outcomes between cohorts. Results: Following PSM, two balanced cohorts of 724 patients who were on ICS and 724 patients who were not on ICS were compared. The use of an ICS was associated with a significantly higher risk of developing ICI pneumonitis within the first year of ICI treatment (RR = 1.379 [95% CI, 1.101-1.728]). ICS use was associated with a reduction in one-year mortality (HR = 0.813 [95% CI, 0.676-0.977], p =0.027). There were no significant differences in infections between the two groups (RR = 1.152 [95% CI, 0.998-1.329]). Conclusions: For patients with COPD and lung cancer treated with ICIs, ICS use was associated with an increased risk of ICI pneumonitis at one year and a reduction in mortality, without a significant difference in risk for infection. Taken together, this study suggests that the incorporation of an ICS in the management of COPD for patients also on ICI for lung cancer may have survival benefit without an added risk of infection. However, careful consideration and vigilant monitoring are required for patients on an ICS given the increased risk of ICI pneumonitis.