Risk factors for pneumonitis in advanced extrapulmonary cancer patients treated with immune checkpoint inhibitors

Abstract

Background Immune-mediated pneumonitis has a high mortality rate; however, little is known about the related risk factors. We analyzed the risk factors for pneumonitis, such as smoking and lung metastasis (LM), among extrapulmonary primary tumors. Methods We retrospectively collected data of 110 patients treated with immune checkpoint inhibitors (ICIs) (nivolumab/pembrolizumab) for extrapulmonary primary tumors at the Shiga University of Medical Science Hospital, between January 2015 and December 2019. The frequency of pneumonitis was evaluated based on the time between the start of ICI treatment and the onset of symptomatic or all pneumonitis. The severity of pneumonitis was graded according to the Common Terminology Criteria for Adverse Events, version 5.0. We analyzed the risk factors, such as the absence or presence of interstitial lung disease (ILD) and lung metastases (LMs), or other clinical factors, including smoking status before ICI administration. Results The Cox proportional hazards regression analysis revealed that the smoking index and presence of ILD were significant factors for an increased rate of all pneumonitis (hazard ratio [HR] = 20.3, 95% confidence interval [CI] = 20.0–20.4; p = 0.02 and HR = 4.3, 95% CI = 1.2–12.1; p = 0.03, respectively). LM was significantly related to an increased rate of symptomatic pneumonitis (HR = 6.8, 95% CI = 1.3–124.2; p = 0.02). Conclusions Smoking index and ILD were the significant risk factors for ICI-induced pneumonitis. LM was a significant risk factor for ICI-induced symptomatic pneumonitis. Therefore, pre-screening for ILD and LM and the recognition of patients’ smoking histories are important for determining the risk of ICI-induced pneumonitis and allowing safe ICI administration.