Outcome and risk factor of immune‐related adverse events and pneumonitis in patients with advanced or postoperative recurrent non‐small cell lung cancer treated with immune checkpoint inhibitors

BACKGROUND: Non‐small cell lung cancer (NSCLC) patients with pre‐existing respiratory diseases have been excluded in clinical trials of immune checkpoint inhibitor (ICI) therapy, and it is unknown whether the same degree of response can be expected as that in patients without pre‐existing respiratory diseases and if they are associated with increased risk for various immune‐related adverse events (irAEs) and ICI pneumonitis. This study aimed to evaluate predictive factors of clinical response, prognostic factors, risk factors of irAEs, and ICI pneumonitis in NSCLC patients with or without pre‐existing respiratory diseases. METHODS: We conducted a retrospective study of 180 NSCLC patients who received ICI monotherapy of nivolumab, pembrolizumab, or atezolizumab from 1 January 2016 to 31 March 2019. RESULTS: A total of 119 patients had pre‐existing respiratory diseases, including 20 with pre‐existing idiopathic interstitial pneumonias (IIPs). A total of 85 patients experienced irAEs, of which ICI pneumonitis was the most frequent adverse event, occurring in 27 patients. Of the three patients who died from irAEs, all from ICI pneumonitis, two had pulmonary emphysema and one had pre‐existing IIP. In multivariate analyses, irAEs were associated with objective response rate (ORR) and favorable OS, and IIPs were associated with increased risk for ICI pneumonitis. However, IIPs were not associated with low ORR or poor OS. CONCLUSIONS: Pre‐existing IIPs were a risk factor for ICI pneumonitis. However, this study showed that ICI therapy can be offered to patients with pre‐existing respiratory diseases with the expectation of the same degree of response as that in patients without pre‐existing respiratory diseases. KEY POINTS: Significant findings of the study: Pre‐existing IIPs were a risk factor for ICI pneumonitis, but objective response rate and prognosis of patients with IIPs were similar to those of other patients. What this study adds: In patients with pre‐existing IIPs, ICI pneumonitis should be noted. However, ICI therapy can be offered to patients with pre‐existing respiratory diseases with the expectation of the same degree of response as that in patients without pre‐existing respiratory diseases