Peripheral blood markers predictive of outcome and immune-related adverse events in advanced non-small cell lung cancer treated with PD-1 inhibitors

Cancer Immunol Immunother. 2020 Sep;69(9):1813-1822. doi: 10.1007/s00262-020-02585-w. Epub 2020 Apr 29.

Abstract

Background: Selected patients with advanced non-small cell lung cancer (NSCLC) benefit from immunotherapy, especially immune checkpoint inhibitors such as PD-1 (programmed cell death protein 1) inhibitor. Peripheral blood biomarkers would be most convenient to predict treatment outcome and immune-related adverse events (irAEs) in candidate patients. This study explored associations between inflammation-related peripheral blood markers and onset of irAEs and outcome in patients with advanced NSCLC receiving PD-1 inhibitors.

Methods: A retrospective analysis was conducted of 102 patients with advanced NSCLC receiving PD-1 inhibitors from January 2017 to May 2019. Cox regression models were employed to assess the prognostic effect of low/high neutrophil/lymphocyte ratio (NLR), lactate dehydrogenase (LDH), and prognostic nutrition index (PNI) on overall survival (OS) and progression-free survival (PFS). Logistic regression models were used to analyze the correlation between peripheral blood markers and the onset of irAEs.

Result: NLR < 5, LDH < 240 U/L, or PNI ≥ 45 was favorably associated with significantly better outcomes compared with higher, higher, or lower values, respectively. The multivariate analysis determined that these parameters were independently associated with both better PFS (p = 0.049, 0.046, 0.014, respectively) and longer OS (p = 0.007, 0.031, < 0.001, respectively). Patients with three favorable factors among NLR, LDH, and PNI had better PFS and OS than did those with two, one, or none. PNI and NLR were associated with the onset of irAEs.

Conclusion: In patients with advanced NSCLC treated with PD-1 inhibitors, pretreatment NLR, LDH, and PNI may be useful predictive markers of clinical outcome and irAEs.

Keywords: Immune-related adverse events; Immunotherapy; Lactate dehydrogenase; Lung cancer; Neutrophil-to-lymphocyte ratio; Prognostic nutrition index.

MeSH terms

  • Antineoplastic Agents / immunology
  • Antineoplastic Agents / therapeutic use*
  • Biomarkers, Tumor / blood*
  • Carcinoma, Non-Small-Cell Lung / blood*
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / immunology*
  • Female
  • Humans
  • Immunotherapy / methods
  • Lung Neoplasms / blood*
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / immunology
  • Lymphocyte Count / methods
  • Lymphocytes / drug effects
  • Lymphocytes / immunology
  • Male
  • Middle Aged
  • Neutrophils / drug effects
  • Neutrophils / immunology
  • Prognosis
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors*
  • Progression-Free Survival
  • Retrospective Studies
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor