Neutrophil-lymphocyte ratio as a predictive biomarker for response to high dose interleukin-2 in patients with renal cell carcinoma

James A. Kuzman, David D. Stenehjem, Joseph Merriman, Archana M. Agarwal, Shiven B. Patel, Andrew W. Hahn, Anitha Alex, Dan Albertson, David M. Gill, Neeraj Agarwal

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Background: Immunotherapy with high-dose interleukin-2 (HD-IL2) results in long-term survival in some metastatic renal cell carcinoma (mRCC) patients but has significant acute toxicities. Biomarkers predicting response to therapy are needed to better select patients most likely to benefit. NLR (absolute neutrophil count (ANC)/absolute lymphocyte count (ALC)) is a prognostic and predicative biomarker in various malignancies. The goal was to determine whether NLR can predict response to HD-IL2 in this setting. Methods: Patients with clear cell mRCC treated with HD-IL2 were identified from an institutional database from 2003-2012. Baseline variables for the assessment of IMDC risk criteria, and neutrophil and lymphocyte count, were collected. Best response criteria were based on RECIST 1.0. Wilcoxon rank-sum test was used to evaluate the association of continuous baseline variables with disease control. NLR was stratified by ≤4 or >4. Progression free survival (PFS) and overall survival (OS) were estimated with the Kaplan-Meier method and Cox proportional hazard models assessed associations of NLR with survival. Results: In 71 eligible patients, median NLR in those with an objective response (n = 14, 20%) was 2.3 vs 3.4 in those without (n = 57, 80%, p = 0.02). NLR ≤4 was associated with improved progression free and overall survival. After adjustment for IMDC risk criteria, NLR remained a significant predictor of OS (ANC/ALC ≤4 vs >4, HR 0.41, 95% CI 1.09-5.46, p = 0.03; ANC/ALC continuous variable per unit change in NLR, HR 1.08, 95% CI 1.01-1.14, p = 0.03). Conclusions: In this discovery set, NLR predicts overall survival in patients treated with HD-IL2 in mRCC, and may allow better patient selection in this setting. Data needs validation in an independent cohort.

Original languageEnglish (US)
Article number1
JournalBMC Urology
Issue number1
StatePublished - Jan 5 2017



  • High dose interleukin-2
  • Neutrophil lymphocyte ratio
  • Renal cell carcinoma

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Kuzman, J. A., Stenehjem, D. D., Merriman, J., Agarwal, A. M., Patel, S. B., Hahn, A. W., Alex, A., Albertson, D., Gill, D. M., & Agarwal, N. (2017). Neutrophil-lymphocyte ratio as a predictive biomarker for response to high dose interleukin-2 in patients with renal cell carcinoma. BMC Urology, 17(1), [1].