| Peer-Reviewed

Prognostic and Predictive Role of Neutrophil to lymphocyte Ratio in Second Line Immunotherapy of Non-small Cell Lung Cancer

Received: 11 May 2021    Accepted: 27 May 2021    Published: 28 June 2021
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Abstract

Background: Programmed death-ligand 1 (PD-L1) expression at immunohistochemistry is the only approved, but still unsatisfactory, biomarker for immunotherapy in Non-Small Cell Lung Cancer (NSCLC). Neutrophil to Lymphocyte ratio (NLR) is a surrogate of systemic inflammation and could correlate with outcome to immunotherapy. This retrospective study (NCT03816657) explored the role of NLR in predicting benefit to nivolumab and susceptibility to hyperprogression (HPD). Methods: PD-L1, baseline and on-therapy NLR values were available in 173NSCLC patients receiving nivolumab. PD-L1 positivity was defined as expression on ≥1% of tumor cells; NLR was dichotomized in high (≥5) or low (<5). Patients were divided in 4 cohorts: 1 (PD-L1+/low NLR), 2 (PD-L1-/high NLR), 3 (PD-L1+/high NLR), 4 (PD-L1-/low NLR). A landmark analysis explored the impact of cohorts and NLR change on objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and its influence on HPD. Results: PD-L1 was positive in 48% and negative in 52% of cases. Pre-treatment NLR was ≥5in 42% and <5 in 58%of patients; on-treatment NLR was ≥5in approximately 50% of patients. PD-L1 positivity was not associated with outcome. Both high pre- and on-therapy NLR was a negative predictor of ORR (p=0.004), PFS (p<0.0001) and OS (p<0.0001). High NLR cohorts (2 and 4) showed poorer outcome than low NLR cohorts. Relative NLR excursion ≥25% at 4 weeks from nivolumab start was associated with reduced PFS and OS, while its decrease or stability was associated with improved outcomes. Although NLR value and its dynamic did not influence HPD occurrence (p=0.062), 53% of hyperprogressors belonged to high NLR cohorts. Conclusion: The current retrospective analysis supports the role of high NLR as a independent negative predictive factor. Its increment during immunotherapy may identify patients with low likelihood of response to immunotherapy.

Published in International Journal of Clinical Oncology and Cancer Research (Volume 6, Issue 2)
DOI 10.11648/j.ijcocr.20210602.16
Page(s) 98-108
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2021. Published by Science Publishing Group

Keywords

Non-small Cell Lung Cancer, Programmed Death Ligand 1, Neutrophil to Lymphocyte Ratio, Nivolumab, Hyperprogression

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Cite This Article
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    Chiara Bennati, Manolo D’Arcangelo, Alessio Gili, Federica Gazzaneo, Sara Pini, et al. (2021). Prognostic and Predictive Role of Neutrophil to lymphocyte Ratio in Second Line Immunotherapy of Non-small Cell Lung Cancer. International Journal of Clinical Oncology and Cancer Research, 6(2), 98-108. https://doi.org/10.11648/j.ijcocr.20210602.16

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    ACS Style

    Chiara Bennati; Manolo D’Arcangelo; Alessio Gili; Federica Gazzaneo; Sara Pini, et al. Prognostic and Predictive Role of Neutrophil to lymphocyte Ratio in Second Line Immunotherapy of Non-small Cell Lung Cancer. Int. J. Clin. Oncol. Cancer Res. 2021, 6(2), 98-108. doi: 10.11648/j.ijcocr.20210602.16

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    AMA Style

    Chiara Bennati, Manolo D’Arcangelo, Alessio Gili, Federica Gazzaneo, Sara Pini, et al. Prognostic and Predictive Role of Neutrophil to lymphocyte Ratio in Second Line Immunotherapy of Non-small Cell Lung Cancer. Int J Clin Oncol Cancer Res. 2021;6(2):98-108. doi: 10.11648/j.ijcocr.20210602.16

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  • @article{10.11648/j.ijcocr.20210602.16,
      author = {Chiara Bennati and Manolo D’Arcangelo and Alessio Gili and Federica Gazzaneo and Sara Pini and Antonello Menghi and Marco Montanari and Giorgio Papiani and Valentina Mazza and Simona Scodes and Michela Spreafico and Giulio Rossi and Dora Caruso and Guido Bellezza and Martina Mandarano and Stefano Tamberi},
      title = {Prognostic and Predictive Role of Neutrophil to lymphocyte Ratio in Second Line Immunotherapy of Non-small Cell Lung Cancer},
      journal = {International Journal of Clinical Oncology and Cancer Research},
      volume = {6},
      number = {2},
      pages = {98-108},
      doi = {10.11648/j.ijcocr.20210602.16},
      url = {https://doi.org/10.11648/j.ijcocr.20210602.16},
      eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ijcocr.20210602.16},
      abstract = {Background: Programmed death-ligand 1 (PD-L1) expression at immunohistochemistry is the only approved, but still unsatisfactory, biomarker for immunotherapy in Non-Small Cell Lung Cancer (NSCLC). Neutrophil to Lymphocyte ratio (NLR) is a surrogate of systemic inflammation and could correlate with outcome to immunotherapy. This retrospective study (NCT03816657) explored the role of NLR in predicting benefit to nivolumab and susceptibility to hyperprogression (HPD). Methods: PD-L1, baseline and on-therapy NLR values were available in 173NSCLC patients receiving nivolumab. PD-L1 positivity was defined as expression on ≥1% of tumor cells; NLR was dichotomized in high (≥5) or low (Results: PD-L1 was positive in 48% and negative in 52% of cases. Pre-treatment NLR was ≥5in 42% and Conclusion: The current retrospective analysis supports the role of high NLR as a independent negative predictive factor. Its increment during immunotherapy may identify patients with low likelihood of response to immunotherapy.},
     year = {2021}
    }
    

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  • TY  - JOUR
    T1  - Prognostic and Predictive Role of Neutrophil to lymphocyte Ratio in Second Line Immunotherapy of Non-small Cell Lung Cancer
    AU  - Chiara Bennati
    AU  - Manolo D’Arcangelo
    AU  - Alessio Gili
    AU  - Federica Gazzaneo
    AU  - Sara Pini
    AU  - Antonello Menghi
    AU  - Marco Montanari
    AU  - Giorgio Papiani
    AU  - Valentina Mazza
    AU  - Simona Scodes
    AU  - Michela Spreafico
    AU  - Giulio Rossi
    AU  - Dora Caruso
    AU  - Guido Bellezza
    AU  - Martina Mandarano
    AU  - Stefano Tamberi
    Y1  - 2021/06/28
    PY  - 2021
    N1  - https://doi.org/10.11648/j.ijcocr.20210602.16
    DO  - 10.11648/j.ijcocr.20210602.16
    T2  - International Journal of Clinical Oncology and Cancer Research
    JF  - International Journal of Clinical Oncology and Cancer Research
    JO  - International Journal of Clinical Oncology and Cancer Research
    SP  - 98
    EP  - 108
    PB  - Science Publishing Group
    SN  - 2578-9511
    UR  - https://doi.org/10.11648/j.ijcocr.20210602.16
    AB  - Background: Programmed death-ligand 1 (PD-L1) expression at immunohistochemistry is the only approved, but still unsatisfactory, biomarker for immunotherapy in Non-Small Cell Lung Cancer (NSCLC). Neutrophil to Lymphocyte ratio (NLR) is a surrogate of systemic inflammation and could correlate with outcome to immunotherapy. This retrospective study (NCT03816657) explored the role of NLR in predicting benefit to nivolumab and susceptibility to hyperprogression (HPD). Methods: PD-L1, baseline and on-therapy NLR values were available in 173NSCLC patients receiving nivolumab. PD-L1 positivity was defined as expression on ≥1% of tumor cells; NLR was dichotomized in high (≥5) or low (Results: PD-L1 was positive in 48% and negative in 52% of cases. Pre-treatment NLR was ≥5in 42% and Conclusion: The current retrospective analysis supports the role of high NLR as a independent negative predictive factor. Its increment during immunotherapy may identify patients with low likelihood of response to immunotherapy.
    VL  - 6
    IS  - 2
    ER  - 

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Author Information
  • Department of Oncology-Hematology, AUSL della Romagna, Santa Maria delle Croci Hospital, Ravenna, Italy

  • Department of Oncology-Hematology, AUSL della Romagna, Santa Maria delle Croci Hospital, Ravenna, Italy

  • Department of Medicine and Surgery, University of Perugia, Perugia, Italy

  • Department of Oncology-Hematology, AUSL della Romagna, Santa Maria delle Croci Hospital, Ravenna, Italy

  • Department of Oncology-Hematology, AUSL della Romagna, Santa Maria delle Croci Hospital, Ravenna, Italy

  • Department of Oncology-Hematology, AUSL della Romagna, Santa Maria delle Croci Hospital, Ravenna, Italy

  • Department of Oncology-Hematology, AUSL della Romagna, Santa Maria delle Croci Hospital, Ravenna, Italy

  • Department of Oncology-Hematology, AUSL della Romagna, Santa Maria delle Croci Hospital, Ravenna, Italy

  • Department of Oncology-Hematology, AUSL della Romagna, Santa Maria delle Croci Hospital, Ravenna, Italy

  • Department of Oncology-Hematology, AUSL della Romagna, Santa Maria delle Croci Hospital, Ravenna, Italy

  • Unit of Biostatistics and Clinical Trials, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), IRCCS, Meldola (FC), Italy

  • Operative Unit of Pathology, AUSL della Romagna, Santa Maria delle Croci Hospital, Ravenna, Italy

  • Operative Unit of Pathology, AUSL della Romagna, Santa Maria delle Croci Hospital, Ravenna, Italy

  • Department of Medicine and Surgery, Section of Anatomic Pathology and Histology, University of Perugia, Perugia, Italy

  • Department of Medicine and Surgery, Section of Anatomic Pathology and Histology, University of Perugia, Perugia, Italy

  • Department of Oncology-Hematology, AUSL della Romagna, Santa Maria delle Croci Hospital, Ravenna, Italy

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