Real-World Evaluation of the Immune Checkpoint Inhibitor Score (IChIS) in Advanced Non-Small Cell Lung Cancer Treated with Immunotherapy

Abstract

Background: The Immune Checkpoint Inhibitor Score (IChIS), an inflammation-based biomarker incorporating neutrophil and immature granulocyte counts, was recently developed to predict outcomes in patients with advanced non-small cell lung cancer (NSCLC) receiving immune checkpoint inhibitors (ICIs). However, evidence regarding its prognostic performance in independent real-world populations remains limited. We aimed to evaluate the prognostic significance of IChIS in a real-world cohort of patients with advanced NSCLC treated with immunotherapy. Methods: This retrospective single-center cohort study included 169 patients with advanced, recurrent, or metastatic NSCLC who received ICIs with palliative intent between September 2022 and December 2025. IChIS ranged from 0 to 2 and was analyzed as a categorical variable, with IChIS 0 as the reference category. The primary endpoint was progression-free survival (PFS), while overall survival (OS) was evaluated as a secondary exploratory endpoint. Survival outcomes were estimated using the Kaplan–Meier method and evaluated using Cox proportional hazards regression. Multivariable models included ICI treatment line as a clinically relevant potential confounder. Results: A total of 169 patients were included. The median follow-up was 14.1 months. IChIS 0, 1, and 2 were observed in 105 (62.1%), 33 (19.5%), and 31 (18.4%) patients, respectively. Median PFS decreased across increasing IChIS categories. In multivariable Cox regression analysis, compared with IChIS 0, both IChIS 1 (adjusted HR 1.61, 95% CI 1.00–2.59; p = 0.04) and IChIS 2 (adjusted HR 3.63, 95% CI 2.22–5.92; p < 0.001) were independently associated with shorter PFS. For OS, IChIS 1 was not significantly associated with outcome (adjusted HR 1.51, 95% CI 0.86–2.64; p = 0.15), whereas IChIS 2 was independently associated with shorter OS (adjusted HR 4.40, 95% CI 2.53–7.64; p < 0.001). Conclusions: Higher IChIS was independently associated with shorter PFS in patients with advanced NSCLC receiving ICIs, supporting its potential role as a simple and readily available prognostic biomarker. The association with OS was primarily observed in patients with IChIS 2 and should be interpreted cautiously given the relatively short follow-up. Prospective multicenter validation is warranted.