Baseline neutrophil-to-eosinophil-ratio and outcome in metastatic clear-cell renal cell carcinoma treated with nivolumab or ipilimumab/nivolumab

Authors

  • Yana Beulque Department of General Medical Oncology, University Hospitals Leuven, Leuven, Belgium
  • Lisa Kinget Department of General Medical Oncology, University Hospitals Leuven, Leuven, Belgium
  • Eduard Roussel Department of Urology, University Hospitals Leuven, Leuven, Belgium
  • Sajedeh Mobaraki Department of General Medical Oncology, University Hospitals Leuven, Leuven, Belgium
  • Annouschka Laenen Biostatistics and Statistical Bioinformatics Center, Leuven
  • Philip R. Debruyne Department of General Medical Oncology, AZ Groeninge, Kortrijk, Belgium; Medical Technology Research Centre (MTRC), School of Life Sciences, Anglia Ruskin University, Cambridge, UK; School of Nursing and Midwifery, University of Plymouth, Plymouth, UK
  • Yannick Van Herck Department of General Medical Oncology, University Hospitals Leuven, Leuven, Belgium
  • Marcella Baldewijns Department of Pathology, University Hospitals Leuven, Leuven, Belgium
  • Agnieszka Wozniak Laboratory of Experimental Oncology, KU Leuven, Leuven, Belgium
  • Abhishek D. Garg Laboratory of Cell Stress & Immunity (CSI), Department of Cellular & Molecular Medicine, KU Leuven, Leuven, Belgium.
  • Jessica Zucman-Rossi Inserm, UMRS-1138, Génomique fonctionnelle des tumeurs solides, Centre de recherche des Cordeliers, Paris, France
  • Gabrielle Couchy Inserm, UMRS-1138, Génomique fonctionnelle des tumeurs solides, Centre de recherche des Cordeliers, Paris, France
  • Maarten Albersen Department of Urology, University Hospitals Leuven, Leuven, Belgium
  • Liesbeth De Wever Department of Radiology, University Hospitals Leuven, Leuven, Belgium
  • Lorenz Haaker Department of Medical Oncology, AZ Sint Lucas, Brugge, Belgium
  • Benoit Beuselinck Department of General Medical Oncology, University Hospitals Leuven, Leuven, Belgium

DOI:

https://doi.org/10.2340/1651-226X.2024.40390

Keywords:

renal cell carcinoma, neutrophil-to-eosinophil ratio, checkpoint inhibitor, immunotherapy, biomarker

Abstract

Background and purpose: This study aims to evaluate neutrophil-to-eosinophil ratio (NER) as a prognostic and/or predictive biomarker in metastatic clear cell renal cell carcinoma (m-ccRCC) treated with nivolumab or ipilimumab/nivolumab.

Patients/materials and methods: We performed a retrospective study on m-ccRCC patients treated with nivolumab or ipilimumab/nivolumab (2012–2022). Baseline NER was calculated and correlated with clinical outcomes: response rate (RR), progression free survival (PFS) and overall survival (OS). Corresponding transcriptomic data were analysed.

Results: We included 201 m-ccRCC patients, 76 treated with ipilimumab/nivolumab and 125 with nivolumab. Baseline NER was statistically significantly associated with International Metastatic RCC Database Consortium (IMDC) risk groups. Increased NER was associated with shorter PFS and OS in the total patient series and nivolumab-treated patients. In patients treated with ipilimumab/nivolumab, increased NER was only statistically significantly associated with shorter OS. The impact of baseline NER on PFS and OS was independent of IMDC risk stratification. No clear correlation was found between baseline NER and RECIST response or maximal tumour shrinkage. In two additional databases, NER was also associated with PFS and OS in first-line vascular-endothelial-growth-factor-receptor tyrosine-kinase-inhibitors (VEGFR-TKIs), but not to disease-free survival in the post-nephrectomy setting. Lower NER was associated with intratumoural molecular features possibly associated with better outcome on immune checkpoint inhibitors.

Interpretation: Lower baseline NER is associated with better PFS and OS, independent of IMDC risk score, in m-ccRCC patients treated with ipilimumab/nivolumab or nivolumab. It correlates with intratumoural molecular features possibly associated with better outcome on immune checkpoint inhibitors. The predictive power of this biomarker is probably limited and insufficient for patient selection.

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2024-08-11

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Beulque, Y., Kinget, L., Roussel, E., Mobaraki, S., Laenen, A., Debruyne, P. R., … Beuselinck, B. (2024). Baseline neutrophil-to-eosinophil-ratio and outcome in metastatic clear-cell renal cell carcinoma treated with nivolumab or ipilimumab/nivolumab. Acta Oncologica, 63(1), 658–668. https://doi.org/10.2340/1651-226X.2024.40390

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Vol. 63 (2024): Acta Oncologica

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Copyright (c) 2023 Yana Beulque, Lisa Kinget, Eduard Roussel, Sajedeh Mobaraki, Annouschka Laenen, Philip R. Debruyne, Yannick Van Herck, Marcella Baldewijns, Agnieszka Wozniak, Abhishek D. Garg, Jessica Zucman-Rossi, Gabrielle Couchy, Maarten Albersen, Liesbeth De Wever, Lorenz Haaker, Benoit Beuselinck

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