Identifying Early Predictive Markers for Immune-Related Adverse Events in Nivolumab-Treated Patients with Renal Cell Carcinoma and Gastric Cancer.

Shinya Takada,Kozo Mino,Maki Yanase,Harabayashi Toru,Kengo Umehara,Tamotsu Sagawa,Maruyama Satoru,Hidetaka Murooka,Hirokazu Hashishita,Koshi Fujikawa,Hideki Sato,Kanae Tahatsu

doi:10.31557/apjcp.2022.23.2.695

Abstract

Background:Neutrophil-to-lymphocyte (NLR) and platelet-to-lymphocyte (PLR) ratios can indicate poor disease prognosis and are inflammation markers. We investigated the role of NLR and PLR as effective predictive markers of immune-related adverse event (irAE) onset in patients treated with nivolumab. Methods:We retrospectively analysed 73 gastric and renal cancer patients treated with nivolumab at the Hokkaido Cancer Centre from January 2017 to June 2020. NLR and PLR were calculated at the initiation of nivolumab treatment and irAE onset. We identified the risk factors for Grade 3-4 irAE onset using NLR, PLR, sex, cancer type, and age. Overall survival (OS) and progression free survival (PFS) were calculated from the initiation of nivolumab treatment to the date of death or censored at last follow-up. Results:Among the 73 patients included, 17 (18%) had at least one grade3-4 irAE. Multivariable logistic regression analyses revealed that pretreatment NLR<4.3 was significantly associated with a reduced risk for onset of grade3-4 irAEs, whereas rate of NLR change after treatment, ΔNLR>120% was significantly associated with an increased risk. Conclusions:NLR is an effective marker for prognosis and onset of grade 3-4 irAEs.

Highlights

Immune checkpoint inhibitors (ICIs) are currently being used in the treatment of a variety of cancers
Our results collectively provide convincing evidence for the use of NLR and PLR as prognostic and predictive markers for immune-related adverse event (irAE) onset in response to nivolumab treatment in cancer patients
Associated risk factors such as a history of autoimmune disease are known, biochemical markers that can predict the risk of irAEs associated with nivolumab treatment have not yet been identified (Hopkins et al, 2017; Champiat et al, 2016)

Summary

Introduction

Immune checkpoint inhibitors (ICIs) are currently being used in the treatment of a variety of cancers. As inflammation markers, NLR and PLR were used to identify tumour-related inflammation (Kiriu et al, 2018; Li et al, 2019; Khunger et al, 2018; Scilla et al, 2017; Katayama et al, 2019). They were proposed as simple indicators of the systemic inflammatory response in critically ill patients of breast, colon, and lung cancer (Zahorec et al, 2001). We investigated the role of NLR and PLR as effective predictive markers of immune-related adverse event (irAE) onset in patients treated with nivolumab. Conclusions: NLR is an effective marker for prognosis and onset of grade 3-4 irAEs

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