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Impact of lymphopenia on efficacy of nivolumab in head and neck cancer patients

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European Archives of Oto-Rhino-Laryngology Aims and scope Submit manuscript

Abstract

Introduction

Lymphopenia has been correlated with poorer survival in patients with metastatic cancers treated with anti-PD-1 immunotherapy. Treatments such as chemotherapy, surgery or radiotherapy can induce lymphopenia. Radiation-induced lymphopenia is common and prolonged in head and neck cancer (HNSCC) patients. We evaluated the impact of lymphopenia, on efficacy of anti PD-1 nivolumab immunotherapy in HNSCC patients.

Methods

a multicenter retrospective study included consecutive patients treated with nivolumab for recurrent/metastatic (R/M) HNSCC between January 2017 and June 2019. Lymphopenia was defined as lymphocyte counts below 1000 cells/mm3 upon initiation of nivolumab. Logistical regression was performed on factors associated with lymphopenia and ROC analyses assessed association between lymphopenia and survival.

Results

median age was 65. Of the 100 included patients, 60% had been treated by surgery, 67% had had first-line chemotherapy, and 89% loco-regional radiotherapy, 65% had concurrent chemotherapy with radiotherapy. Lymphopenia occurred in 56 (56%) patients upon initiation of nivolumab, with 29 (29%) patients having radiation-related lymphopenia. Prior locoregional radiotherapy was the only factor associated with lymphopenia upon initiation of nivolumab by logistical regression (OR 0.144 [0.029–0.706], p − 0.017). Lymphopenia upon initiation of nivolumab did not affect progression-free survival (PFS) (p − 0.815), overall survival (OS) (p − 0.783) or disease control rate (DCR) (p − 0.125). Locoregional symptomatology (HR − 2.37 [1.24–4.54], p − 0.009), metastatic symptomatology (HR − 4.74 [2.21–10.15], and persistent lymphopenia under nivolumab (HR 3.96 [1.19–13.17] p − 0.034) were associated with poorer OS in multivariate analysis.

Conclusions

Lymphopenia upon initiation of nivolumab was not associated with poorer survival in R/M HNSCC patients, but persistence of lymphopenia during immunotherapy might be a prognostic marker of patient survival.

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Data availability

The participants of this study did not give written consent for their data to be shared publicly, so due to the sensitive nature of the research supporting data is not available.

Abbreviations

5-FU:

5-Fluoro-uracile

BMI:

Body mass index

CPS:

Combined positive score

DCR:

Disease control rate

HNSCC:

Head and neck cancer

ICI:

Immune check-point inhibitors

NLR:

Neutrophil-to-lymphocyte ratio

OS:

Overall survival

PD-1:

Programmed cell death protein 1

PD-L1:

Programmed cell death ligand 1

PFS:

Progression-free survival

R/M:

Recurrent/metastatic

WHO:

World Health Organization

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Authors and Affiliations

  1. Department of Radiotherapy, Center François Baclesse, Caen, France

    Mathieu Césaire & Juliette Thariat

  2. Department of Medical Oncology, Center François Baclesse, Caen, France

    Audrey Rambeau & Alisson Johnson

  3. Department of Medical Oncology, Center Henri Becquerel, Rouen, France

    Florian Clatot

  4. Normandie University, Rouen, France

    Natacha Heutte

  5. Corpuscular Physics Laboratory IN2P3/ENSICAEN/CNRS UMR 6534, Caen, France

    Juliette Thariat

  6. Normandie University, Caen, France

    Juliette Thariat

Authors
  1. Mathieu Césaire
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  4. Alisson Johnson
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Correspondence to Mathieu Césaire.

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The authors declared no conflicts of interest.

Ethical approval

Our study has received the approval of the CNIL and the Ethics Committee of the François Baclesse Center. A non-opposition briefing note for patients living at the time of inclusion was issued to the various participating centers.

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Césaire, M., Rambeau, A., Clatot, F. et al. Impact of lymphopenia on efficacy of nivolumab in head and neck cancer patients. Eur Arch Otorhinolaryngol 280, 2453–2461 (2023). https://doi.org/10.1007/s00405-022-07800-1

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  • DOI: https://doi.org/10.1007/s00405-022-07800-1

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