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

Asian Pac J Cancer Prev. 2022 Feb 1;23(2):695-701. 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.

Keywords: Immune checkpoint inhibitors; Neutrophils to lymphocytes; immune-related adverse event; platelet to lymphocytes.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Immunological / adverse effects*
  • Biomarkers, Tumor / blood
  • Blood Cell Count*
  • Blood Platelets / metabolism
  • Carcinoma, Renal Cell / blood*
  • Carcinoma, Renal Cell / drug therapy
  • Carcinoma, Renal Cell / immunology
  • Female
  • Humans
  • Kidney Neoplasms / blood*
  • Kidney Neoplasms / drug therapy
  • Kidney Neoplasms / immunology
  • Logistic Models
  • Lymphocytes / metabolism
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neutrophils / metabolism
  • Nivolumab / adverse effects*
  • Predictive Value of Tests
  • Prognosis
  • Progression-Free Survival
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Stomach Neoplasms / blood*
  • Stomach Neoplasms / immunology
  • Survival Rate

Substances

  • Antineoplastic Agents, Immunological
  • Biomarkers, Tumor
  • Nivolumab