Prognostic Impact and Risk Factors of Immune-Related Pneumonitis in Patients With Non-Small-Cell Lung Cancer Who Received Programmed Death 1 Inhibitors

Abstract

Introduction: Pneumonitis is one of the immune-related adverse events of programmed death 1 (PD-1) inhibitors that sometimes cause lethal outcomes. Although some recent reports have described PD-1 inhibitors as more effective in non-small-cell lung cancer (NSCLC) patients with immune-related adverse events than in those without, few data are available on the prognosis of those treated with PD-1 inhibitors who developed immune-related pneumonitis (IRP). Additionally, the robust risk factors of IRP have not been well elucidated.

Patients and methods: A retrospective review of patients with recurrent or advanced NSCLC who took a PD-1 inhibitor (nivolumab or pembrolizumab monotherapy) between January 2016 and March 2018 was undertaken. Radiologic findings such as unilateral infiltration were also defined as IRP as long as they were deemed relevant to PD-1 inhibitors.

Results: Twenty-seven (16%) of 170 patients developed IRP. Although 22 (81%) of 27 patients with IRP recovered with drug cessation with or without corticosteroid therapy, 8-week landmark analysis showed the overall survival after administration of the PD-1 inhibitor was significantly shorter in patients with IRP than in those without (8.7 vs. 23.0 months, P = .015). Patients with IRP tended to not receive next-line treatment and choose best supportive care after cessation of PD-1 inhibitor therapy. In the multivariate analysis, pembrolizumab (vs. nivolumab) and low serum albumin were independent risk factors for IRP.

Conclusion: Development of IRP was correlated with poor prognosis in patients with NSCLC. Further study is necessary for establishing the best prediction and management strategies for IRP.

Keywords: Drug-induced lung disease; Immune checkpoint inhibitor; Immune-related adverse event; PD-1 inhibitor.