C-reactive protein and the neutrophil-to-lymphocyte ratio are prognostic biomarkers in metastatic renal cell carcinoma patients treated with nivolumab

Int J Clin Oncol. 2020 Jan;25(1):135-144. doi: 10.1007/s10147-019-01528-5. Epub 2019 Sep 11.

Abstract

Background: Association between systemic inflammation and clinical outcome of immune checkpoint inhibitors (ICIs) has received focus. Our objective was to evaluate the utility of the neutrophil-to-lymphocyte ratio (NLR) in metastatic renal cell carcinoma (mRCC) patients treated with nivolumab as well as the prognostic impact of the C-reactive protein (CRP) level.

Materials and methods: Sixty-five mRCC patients treated with nivolumab were enrolled. We retrospectively investigated several factors, including the NLR and the CRP level, for their association with progression-free survival (PFS) and overall survival (OS). In addition, we evaluated their impact on the objective response.

Results: The CRP level was confirmed to be positively correlated with the NLR in a correlation analysis. An NLR ≥ 5 was significantly associated with a worse PFS (hazard ratio [HR]: 4.54, 95% confidence interval [CI] 1.93-10.7; p < 0.001), and an NLR ≥ 5 and a CRP ≥ 2.1 mg/dL were identified as a significant factors predicting worse OS with HRs of 4.88 (95% CI 1.35-17.7; p < 0.016) and 3.89 (95% CI 1.01-15.0; p = 0.049), respectively. In addition, patients with a ≥ 25% decrease in the NLR and CRP level showed a significantly better response to nivolumab than those without a ≥ 25% decrease in the NLR and CRP level, with odds ratios of 9.54 (95% CI 2.09-49.8, p = 0.001) and 4.36 (95% CI 1.03-18.9, p = 0.032), respectively.

Conclusion: Both the NLR and CRP levels were significantly associated with the clinical outcome of nivolumab in mRCC patients. The potential prognostic impact of those markers needs to be further prospectively investigated.

Keywords: C-reactive protein (CRP); Immune checkpoint inhibitor (ICI); Metastatic renal cell carcinoma (mRCC); Neutrophil-to-lymphocyte ratio (NLR); Nivolumab; Overall survival (OS).

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Immunological / therapeutic use
  • Biomarkers, Tumor / blood*
  • C-Reactive Protein / analysis*
  • Carcinoma, Renal Cell / blood
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / mortality
  • Carcinoma, Renal Cell / surgery
  • Female
  • Humans
  • Kidney Neoplasms / blood
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / mortality
  • Kidney Neoplasms / surgery
  • Lymphocytes / pathology
  • Male
  • Middle Aged
  • Neutrophils / pathology
  • Nivolumab / therapeutic use*
  • Prognosis
  • Proportional Hazards Models
  • Retrospective Studies
  • Survival Analysis
  • Treatment Outcome

Substances

  • Antineoplastic Agents, Immunological
  • Biomarkers, Tumor
  • Nivolumab
  • C-Reactive Protein