Predictive Factors Correlated with the Development of Immune-Related Adverse Events in Patients with Non-Small Cell Lung Cancer Treated with Immune Checkpoint Inhibitors

Abstract

Kei Sonehara, Kazunari Tateishi, Taisuke Araki, Masamichi Komatsu, Jumpei Akahane, Hiroshi Yamamoto, Masayuki Hanaoka First Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto City, Nagano, JapanCorrespondence: Kazunari TateishiFirst Department of Internal Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto City, Nagano, 390-8621, Japan, Tel [phone], Fax [phone], Email [email protected]: Similar to the neutrophil-to-lymphocyte ratio and lung immune prognostic index (LIPI), immune-related adverse events (irAEs) were favorable prognostic factors in several studies, for patients with non-small cell lung cancer who received immune checkpoint inhibitors (ICIs). However, few studies have investigated patient characteristics and markers that predict the development of irAEs, and factors predicting the development of irAEs have not been clarified. Thus, the present study aimed to examine the predictive factors correlated with the development of irAEs in non-small cell lung cancer (NSCLC) patients who received anti-programmed cell death protein 1/programmed cell death ligand 1 inhibitor monotherapy.Patients and Methods: The present study was retrospectively enrolled 113 advanced NSCLC patients who received ICIs between February 2016 and May 2021 and was conducted at Shinshu University Hospital. All patients were divided into two groups according to with or without of irAEs. We compared the clinical findings and laboratory data between the two groups and considered predictive factors correlated with the development of irAEs.Results: Forty-four (38.9%) patients developed irAEs of any grade. The most common irAEs were hypothyroidism (12.4%), followed by skin rash (7.1%) and interstitial lung disease (7.1%). The survival time in patients with irAEs was significantly more prolonged compared to those without irAEs (median progression-free survival: 6.8 vs 2.1 months, p < 0.001; median overall survival: 25.3 vs 9.6 months, p = 0.001). Multivariate analyses based on logistic regression revealed independent predictive factors that correlated with the development of irAEs to be first-line ICI treatment and a score of 0 or 1 on LIPI.Conclusion: The present study revealed that lines of immunotherapy and LIPI were correlated with the development of irAEs in NSCLC patients who received ICIs and can help clinicians who manage patients experiencing irAEs receiving ICIs.Keywords: non-small cell lung cancer, programmed cell death ligand 1 inhibitor monotherapy, immune-related adverse events, lung immune prognostic index, predictive factor

Keywords

• non-small cell lung cancer
• programmed cell death ligand 1 inhibitor monotherapy
• immune-related adverse events
• lung immune prognostic index
• predictive factor