Association of tumor burden with severe immune-related adverse events in nivolumab plus ipilimumab therapy for non-small cell lung cancer

Abstract Ipilimumab and nivolumab improve the prognosis of patients with non-small cell lung cancer (NSCLC), albeit with a higher incidence of immune-related adverse events (irAEs) than immune checkpoint inhibitor (ICI) monotherapy. In this study, we investigated whether baseline tumor burden is associated with the development of severe irAEs during treatment with ipilimumab plus nivolumab with or without chemotherapy. Consecutive patients with NSCLC receiving nivolumab plus ipilimumab with or without chemotherapy were retrospectively examined at the Hakodate Goryoukaku Hospital between December 2020 and December 2021. Total tumor burden was measured according to the Response Evaluation Criteria in Solid Tumors, version 1.1. We defined irAEs as ICI therapy-related toxicities according to the Common Terminology Criteria for Adverse Events, version 5.0. Tumor burden differed significantly between patients with and without severe irAEs (100 mm vs. 67.5 mm, p = 0.001). A high tumor burden correlated with severe irAEs, independent of the complementary chemotherapy. The multivariate odds ratio of severe irAEs and high tumor burden was 6.72 (95% confidence interval = 2.05–22.0, p = 0.0017). Baseline tumor burden is a potential risk factor for severe irAEs in patients treated with combination ICI therapy; thus, careful monitoring of adverse events is needed.