Correlation of Neutrophil to Lymphocyte Ratio and Absolute Neutrophil Count With Outcomes With PD-1 Axis Inhibitors in Patients With Advanced Non–Small-Cell Lung Cancer

Zer, Alona; Sung, Mike; Walia, P.; Khoja, Leila; Maganti, Manjula; Labbé, Catherine; Shepherd, Frances A.; Bradbury, Penelope Ann; Feld, Ronald; Liu, Geoffrey; Iazzi, Melissa; Zawisza, D.; Nouriany, Nazanin; Leighl, Natasha B.

doi:10.1016/j.cllc.2018.04.008

Cited by 102 publications

(98 citation statements)

References 56 publications

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“…Many studies investigated the prognostic value of NLR since it better reflects the equilibrium between protumor and antitumor activity of the host immune system [46]. NLR has been studied in patients treated with ICIs in different types of cancers and several thresholds have been proposed [47][48][49].…”

Section: Discussionmentioning

confidence: 99%

EPSILoN: A Prognostic Score for Immunotherapy in Advanced Non-Small-Cell Lung Cancer: A Validation Cohort

Prelaj

Ferrara

Rebuzzi

et al. 2019

Cancers

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Background: Beyond programmed death ligand 1 (PD-L1), no other biomarkers for immunotherapy are used in daily practice. We previously created EPSILoN (Eastern Cooperative Oncology Group performance status (ECOG PS), smoking, liver metastases, lactate dehydrogenase (LDH), neutrophil-to-lymphocyte ratio (NLR)) score, a clinical/biochemical prognostic score, in 154 patients treated with second/further-line immunotherapy. This study’s aim was to validate EPSILoN score in a different population group. Methods: 193 patients were included at National Cancer Institute of Milan (second-line immunotherapy, 61%; further-line immunotherapy, 39%). Clinical/laboratory parameters such as neutrophil-to-lymphocyte ratio and lactate dehydrogenase levels were collected. Kaplan–Meier and Cox hazard methods were used for survival analysis. Results: Overall median progression-free survival and median overall survival were 2.3 and 7.6 months, respectively. Multivariate analyses for Progression-Free Survival (PFS) identified heavy smokers (hazard ratio (HR) 0.71, p = 0.036) and baseline LDH < 400 mg/dL (HR 0.66, p = 0.026) as independent positive factors and liver metastases (HR 1.48, p = 0.04) and NLR ≥ 4 (HR 1.49, p = 0.029) as negative prognostic factors. These five factors were included in the EPSILoN score which was able to stratify patients in three different prognostic groups, high, intermediate and low, with PFS of 6.0, 3.8 and 1.9 months, respectively (HR 1.94, p < 0.001); high, intermediate and low prognostic groups had overall survival (OS) of 24.5, 8.9 and 3.4 months, respectively (HR 2.40, p < 0.001). Conclusions: EPSILoN, combining five baseline clinical/blood parameters (ECOG PS, smoking, liver metastases, LDH, NLR), may help to identify advanced non-small-cell lung cancer (aNSCLC) patients who most likely benefit from immune checkpoint inhibitors (ICIs).

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Section: Discussionmentioning

confidence: 99%

EPSILoN: A Prognostic Score for Immunotherapy in Advanced Non-Small-Cell Lung Cancer: A Validation Cohort

Prelaj

Ferrara

Rebuzzi

et al. 2019

Cancers

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“…The dynamics of NLR and ANC during nivolumab treatment may be associated with the efficacy of the subsequent salvage chemotherapy. Many studies have shown that low baseline NLR and ANC predict the efficacy of nivolumab therapy in various cancers . More recent studies have shown that an early decrease in NLR during treatment with PD‐1 inhibitors predicts its efficacy .…”

Section: Discussionmentioning

confidence: 99%

“…Many studies have shown that low baseline NLR and ANC predict the efficacy of nivolumab therapy in various cancers . More recent studies have shown that an early decrease in NLR during treatment with PD‐1 inhibitors predicts its efficacy . NLR and ANC have been reported to correlate with the number of circulating MDSCs and tumor‐associated neutrophils, which suppress the function of antitumor T cells .…”

Section: Discussionmentioning

confidence: 99%

“…However, we did not clarify the mechanisms that created these synergistic effects during nivolumab treatment. Several studies have shown that the neutrophil‐to‐lymphocyte ratio (NLR) and the absolute neutrophil count (ANC) in the blood can predict the efficacy of PD‐1 inhibitors in patients with NSCLC . NLR and ANC have also been reported to reflect the number of circulating myeloid‐derived suppressor cells (MDSCs) and tumor‐associated neutrophils, which inhibit the function of antitumor T cells .…”

Section: Introductionmentioning

confidence: 99%

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Dynamics of blood neutrophil‐related indices during nivolumab treatment may be associated with response to salvage chemotherapy for non‐small cell lung cancer: A hypothesis‐generating study

et al. 2018

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Several recent studies have shown that salvage chemotherapy following PD‐1 blockade produces high antitumor activity in some patients with non‐small lung cancer (NSCLC). However, the underlying synergistic mechanisms remain uncertain. The blood neutrophil‐to‐lymphocyte ratio (NLR) and absolute neutrophil count (ANC) can reflect the number of circulating myeloid‐derived suppressor cells and tumor‐associated neutrophils. The immunosuppressive status of the tumor microenvironment could be monitored by the time‐series patterns of NLR and ANC. The dynamics of NLR and ANC during nivolumab treatment were retrospectively explored in 15 patients: 8 patients receiving subsequent salvage chemotherapy (2 groups: 3 non‐responders and 5 responders), and 7 responders to nivolumab alone (2 groups: 4 partial response and 3 complete response). The dynamics of NLR and ANC during nivolumab differed among these four groups (NLR P = 0.045, ANC P = 0.067). NLR and ANC during nivolumab treatment increased over time in non‐responders to salvage chemotherapy, with an inverse relationship between drug response and NLR or ANC at four to six weeks among the four groups. We hypothesize that the early dynamics of NLR and ANC during nivolumab may be associated with the late efficacy of subsequent salvage chemotherapy. Further studies involving a large cohort are needed to confirm these findings, which could provide insight into the role of myeloid immunosuppressor cells in combination PD‐1 blockade and chemotherapy.

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“…Interestingly, emerging evidence suggests that high ANC could be a negative predictor of response to immune checkpoint inhibitors (ICI) for cancer such as lung cancer and melanoma (31–33). By contrast, high TILs are positive predictors of treatment response to ICI (34, 35).…”

Section: Discussionmentioning

confidence: 99%

Associations between absolute neutrophil count and lymphocyte-predominant breast cancer

Yoon

Park

Jin

et al. 2019

Preprint

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2Tumor-infiltrating lymphocytes (TILs) might be associated with host-cell mediated immunity, 3 which could be partly reflected by peripheral blood cell counts. We aimed to investigate 4 whether peripheral blood cell counts are associated with TILs in breast cancer. Between August 5 2016 and July 2018, we evaluated the percentage of stromal TILs in breast cancer patients who 6 underwent primary surgery, using the standardized methodology proposed by the international 7 TIL Working Group. Lymphocyte-predominant breast cancer (LPBC) was defined as tumors 8 having high TIL levels (≥ 50%). Peripheral blood cell counts including absolute neutrophil 9 counts (ANC), absolute lymphocyte counts (ALC) and neutrophil-to-lymphocyte ratio (NLR) 10 was obtained from pretreatment laboratory data. Of the 684 patients, 99 (17.2%) had LPBC, 11 and 478 (82.8%) had non-LBPC. In a comparison of 3 markers of peripheral blood counts, 12 LPBC had a significantly lower mean ANC than non-LPBC (3,330 vs. 3,660; P=0.004), but 13 the other means were not different. Decreasing ANC was an independent clinical factor in 14 predicting LPBC (OR: 0.736, 95% CI: 0.591-0.917; P=0.004). Low peripheral ANC might be 15 linked with LPBC, supporting the hypothesis that systemic immune cell counts might be 16 associated with the tumor-immune microenvironment.

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Correlation of Neutrophil to Lymphocyte Ratio and Absolute Neutrophil Count With Outcomes With PD-1 Axis Inhibitors in Patients With Advanced Non–Small-Cell Lung Cancer

Cited by 102 publications

References 56 publications

EPSILoN: A Prognostic Score for Immunotherapy in Advanced Non-Small-Cell Lung Cancer: A Validation Cohort

EPSILoN: A Prognostic Score for Immunotherapy in Advanced Non-Small-Cell Lung Cancer: A Validation Cohort

Dynamics of blood neutrophil‐related indices during nivolumab treatment may be associated with response to salvage chemotherapy for non‐small cell lung cancer: A hypothesis‐generating study

Associations between absolute neutrophil count and lymphocyte-predominant breast cancer

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