C-reactive protein and the neutrophil-to-lymphocyte ratio are prognostic biomarkers in metastatic renal cell carcinoma patients treated with nivolumab
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.
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.
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.
KeywordsMetastatic renal cell carcinoma (mRCC) Nivolumab Immune checkpoint inhibitor (ICI) Neutrophil-to-lymphocyte ratio (NLR) C-reactive protein (CRP) Overall survival (OS)
Anti-cytotoxic T-lymphocyte antigen-4
Immune checkpoint inhibitor
International metastatic renal cell carcinoma Database Consortium
Immune-related adverse event
Karnofsky performance status
Metastatic renal cell carcinoma
Objective response rate
Anti-programmed death-ligand 1
Multitargeted receptor tyrosine kinase inhibitor
KS, TT and KH designed the study. KS, TT, JF, KH acquired and analyzed the data. KS, TT and KH drafted the manuscript, and JF, NH, YN and MF revised it critically for important intellectual content. All authors gave final approval of the version to be published.
Compliance with ethical standards
Conflict of interest
The authors declare no conflict of interest.
The study design was approved by the Research Ethics Committee of our institution (No. B190059), which was conducted in accordance with the Declaration of Helsinki. Informed consent to participate in the present study was obtained from all patients.
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