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Post-treatment neutrophil-to-lymphocyte ratio at week 6 is prognostic in patients with advanced non-small cell lung cancers treated with anti-PD-1 antibody

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Abstract

We investigated inflammatory markers such as the neutrophil-to-lymphocyte ratio (NLR) that may predict the response to anti-PD-1 (programmed cell death protein 1) antibody therapy. Data from 54 patients with non-small cell lung cancer (NSCLC) treated with anti-PD-1 antibodies were retrospectively analyzed. The NLR was assessed at baseline and 6 weeks after the start of treatment (post-treatment). Eighteen of 54 patients (33.3%) had objective responses to treatment. Older age, absence of brain metastasis, low post-treatment NLR (< 5), and immune-related adverse events were significantly associated with response. Patients with a high post-treatment NLR (≥ 5) had significantly shorter progression-free survival (PFS) than those with a low post-treatment NLR (median, 1.3 vs. 6.1 months, p < 0.001). Multivariate analysis demonstrated that high post-treatment NLR [hazard ratio (HR) 15.1, 95% confidence interval (CI) 1.5–50.1, p < 0.001], liver metastasis (HR 4.9, 95% CI 1.9–12.4, p = 0.001), and brain metastasis (HR 3.2, 95% CI 1.3–8.2, p = 0.013) were independent prognostic factors of shorter PFS. Overall survival (OS) was significantly different in patients with high and low post-treatment NLRs (median, 2.1 vs. 14.0 months, p < 0.001). A high post-treatment NLR remained an independent prognostic factor for OS in multivariate analysis (HR 3.9, 95% CI 1.6–9.2, p = 0.003). The NLR at 6 weeks after treatment initiation was a prognostic marker in patients with advanced NSCLC treated with anti-PD-1 antibody. Further studies are warranted to evaluate the role of the 6-week NLR as a predictor in anti-PD-1 antibody treatment.

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Abbreviations

AE:

Adverse event

ALC:

Absolute lymphocyte counts

ALK:

Anaplastic lymphoma kinase

ANC:

Absolute neutrophil counts

CI:

Confidence interval

CNS:

Central nervous system

CRC:

Colorectal cancer

EGFR:

Epidermal growth factor receptor

HR:

Hazard ratio

IRAE:

Immune-related adverse events

KC:

Kupffer cells

NLR:

Neutrophil-to-lymphocyte ratio

NSCLC:

Non-small cell lung cancer

ORR:

Objective response rate

PHR:

Proportional-hazard regression

PFS:

Progression-free survival

PLR:

Platelet-to-lymphocyte ratio

SII:

Systemic immune-inflammation index

SNUBH:

Seoul National University Bundang Hospital

SNUH:

Seoul National University Hospital

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Author notes

  1. Koung Jin Suh and Se Hyun Kim equally contributed to this work.

Authors and Affiliations

  1. Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, 82, Gumi-ro 173 beon-gil, Bundang-Gu, Seongnam, Gyeonggi-do, 13620, Republic of Korea

    Koung Jin Suh, Se Hyun Kim, Yu Jung Kim & Jong Seok Lee

  2. Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea

    Koung Jin Suh, Miso Kim, Bhumsuk Keam, Tae Min Kim, Dong-Wan Kim & Dae Seog Heo

  3. Seoul National University Cancer Research Institute, Seoul, Republic of Korea

    Bhumsuk Keam, Tae Min Kim, Dong-Wan Kim & Dae Seog Heo

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  1. Koung Jin Suh
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Suh, K.J., Kim, S.H., Kim, Y.J. et al. Post-treatment neutrophil-to-lymphocyte ratio at week 6 is prognostic in patients with advanced non-small cell lung cancers treated with anti-PD-1 antibody. Cancer Immunol Immunother 67, 459–470 (2018). https://doi.org/10.1007/s00262-017-2092-x

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