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Variation in neutrophil to lymphocyte ratio (NLR) as predictor of outcomes in metastatic renal cell carcinoma (mRCC) and non-small cell lung cancer (mNSCLC) patients treated with nivolumab

Cancer Immunology, Immunotherapy volume 69, pages 2513–2522 (2020)Cite this article

Abstract

Background

An elevated pre-treatment neutrophil to lymphocytes ratio (NLR) is associated with poor prognosis in various malignancies. Optimal cut-off is highly variable across studies and could not be determined individually for a patient to inform his prognosis. We hypothesize that NLR variations could be more useful than baseline NLR to predict progression-free survival (PFS) and overall survival (OS) in patients (pts) receiving anti-PD1 treatment.

Patients and methods

All pts with metastatic renal cell carcinoma (mRCC) and metastatic non-small cell lung cancer (mNSCLC) who received anti-PD1 nivolumab monotherapy in second-line setting or later were included in this French multicentric retrospective study. NLR values were prospectively collected prior to each nivolumab administration. Clinical characteristics were recorded. Associations between baseline NLR, NLR variations and survival outcomes were determined using Kaplan–Meier’s method and multivariable Cox regression models.

Results

161 pts (86 mRCC and 75 mNSCLC) were included with a median follow-up of 18 months. On the whole cohort, any NLR increase at week 6 was significantly associated with worse outcomes compared to NLR decrease, with a median PFS of 11 months vs 3.7 months (p < 0.0001), and a median OS of 28.5 months vs. 18 months (p = 0.013), respectively. In multivariate analysis, NLR increase was significantly associated with worse PFS (HR 2.2; p = 6.10−5) and OS (HR 2.1; p = 0.005). Consistent results were observed in each cohort when analyzed separately.

Conclusion

Any NLR increase at week 6 was associated with worse PFS and OS outcomes. NLR variation is an inexpensive and dynamic marker easily obtained to monitor anti-PD1 efficacy.

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Data availability

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Funding

The investigators AS, YA had access to the raw data. All authors approved the final manuscript. The corresponding author had full access to all the data, and takes final responsibility for the manuscript submitted for publication.

Author information

Affiliations

  1. Medical Oncology Department, Hôpital Européen Georges Pompidou, Paris, France

    A. Simonaggio, R. Elaidi, C. Thibault, S. Oudard & Y. A. Vano

  2. Department of Radiology, Hôpital Européen Georges Pompidou, Paris, France

    L. Fournier

  3. Medical Thoracic Oncology Department, Hopital Européen Georges Pompidou, Paris, France

    E. Fabre

  4. Department of Medical Oncology, Centre Antoine Lacassagne, Université Côte d’Azur, Nice, France

    V. Ferrari & D. Borchiellini

  5. Department of Medical Oncology, University Hospital of Strasbourg, Strasbourg, France

    J. Thouvenin & P. Barthelemy

  6. Department of Immunology, Hôpital Européen Georges Pompidou, 75015, Paris, France

    E. Tartour

  7. U970, Université Paris Descartes Sorbonne Paris-Cité, 75006, Paris, France

    E. Fabre & E. Tartour

  8. INSERM, UMR-S 1138, Centre de Recherche des Cordeliers, Team “Cancer, Immune Control and Escape”, University Paris Descartes Sorbonne, 75006, Paris, France

    Y. A. Vano

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Contributions

AS, RE, SO and YAV were involved in the study design and concept. AS, YAV, EF, VF, DB, JT, PB, CT were involved in the identification and selection of patients. AS and RE were involved in the statistical analysis. LF was involved in the radiographic evaluation. All authors were involved in the review and editing of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Y. A. Vano.

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Conflict of interest

YV, SO, CT and PB: consulting fees from BMS, MSD, Pfizer, Novartis, Ipsen, Roche, Astellas, Sanofi, Janssen. DB: funding to institution for clinical research, advisory role or travel accommodation: Bristol-Meyers Squibb, Pfizer, Roche, Ipsen, MSD, Astra-Zeneca. No potential conflicts of interest were disclosed by the other authors.

Ethics approval and consent to participate

The study was approved by the local institutional review board and was conducted with Good Clinical Practice Guidelines and the Declaration of Helsinki. All patients gave their oral consent. CNIL declaration No 2215794 v 0

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Simonaggio, A., Elaidi, R., Fournier, L. et al. Variation in neutrophil to lymphocyte ratio (NLR) as predictor of outcomes in metastatic renal cell carcinoma (mRCC) and non-small cell lung cancer (mNSCLC) patients treated with nivolumab. Cancer Immunol Immunother 69, 2513–2522 (2020). https://doi.org/10.1007/s00262-020-02637-1

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  • DOI: https://doi.org/10.1007/s00262-020-02637-1

Keywords

  • Neutrophil to lymphocyte ratio (NLR)
  • NLR variation
  • Anti-PD1
  • Nivolumab
  • Renal cell carcinoma
  • Non-small cell lung cancer