Risk factors for severe immune-related adverse events after first-line pembrolizumab monotherapy or combination chemotherapy for non-small-cell lung cancer

Summary Pembrolizumab treatment is associated with a favorable prognosis in patients with non-small-cell lung cancer (NSCLC). Here, we investigated the associations among pre-treatment clinical factors, baseline overall tumor burden, and development of severe immune-related adverse events (irAEs; grade ≥ 3) after pembrolizumab treatment with or without chemotherapy. We retrospectively examined consecutive patients with advanced NSCLC who received pembrolizumab with or without chemotherapy at Hakodate Goryoukaku Hospital from March 2017 to February 2021. The baseline overall tumor burden was measured as the sum of the unidimensional diameters of up to five target lesions. We defined irAEs as toxicities related to immune checkpoint inhibitors based on the Common Terminology Criteria for Adverse Events, version 5.0. Tumor burden differed significantly between patients with and without severe irAEs (85 vs. 65 mm, p = 0.0367). The cutoff value for overall tumor burden was set to 80 mm. Good performance status (PS = 0) and PD-L1 expression > 80%, but not overall tumor burden, were correlated with severe irAEs, regardless of complementary chemotherapy. The multivariate odds ratios of good PS and high PD-L1 expression for severe irAEs were 3.27 (95% confidence interval [CI]: 1.22–8.77, p = 0.019) and 4.44 (95% CI: 1.59–12.42, p = 0.0044), respectively. Baseline overall tumor burden, good PS, and high PD-L1 expression were associated with severe irAEs in patients with NSCLC treated with first-line pembrolizumab with or without chemotherapy. Patients with these factors should be carefully monitored to prevent irAEs.