Neutrophil-to-lymphocyte ratio as an early marker of outcomes in patients with advanced non-small-cell lung cancer treated with nivolumab

Nakaya, Aya; Kurata, Takeshi; Yoshioka, Hiroshige; Takeyasu, Yuki; Niki, Maiko; Kibata, Kayoko; Satsutani, Naoko; Ogata, Makoto; Miyara, Takayuki; Nomura, Shosaku

doi:10.1007/s10147-018-1250-2

Cited by 110 publications

(97 citation statements)

References 31 publications

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“…Seven studies 17–19,26,29,30,33 reported number of patients achieved ORR and DCR after treatment of Nivolumab (Supplemental Table 3). In a total of 716 patients, 141 were considered as ORR and 236 as DCR, with percentages of 19.69% and 32.96%, respectively.…”

Section: Combined Resultsmentioning

confidence: 99%

“…38 Meanwhile, Nivolumab and Pembrolizumab are the recently approved immune checkpoint blockades for treating advanced non-small cell lung cancer after failure of traditional chemotherapy or not. 3 Several clinical studies 17,18,20,39 assessed relationship between NLR and immunotherapy, and some of them 17,18,20 argued that NLR could serve as a predictive factor while other found negative results. 39 Could NLR be a candidate for predicating prognosis of Nivolumab in NSCLC?…”

Section: Discussionmentioning

confidence: 99%

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A reliable and feasible way to predict the benefits of Nivolumab in patients with non-small cell lung cancer: a pooled analysis of 14 retrospective studies

Cao

et al. 2018

OncoImmunology

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Objective: Nivolumab has been used for treating non-small cell lung cancer (NSCLC) worldwide. Whether neutrophil-lymphocyte ratio (NLR) can predict the prognosis of NSCLC treated with Nivolumab is still under debate. This meta-analysis was to assess the significance of NLR as a predictive factor in NSCLC patients receiving Nivolumab.Methods: Databases including PubMed, Embase, and the Cochrane library were searched to identify eligible studies evaluating the role of NLR in predicting prognosis of NSCLC treated with Nivolumab until March 2018 without language restrictions. The meta-analysis was performed using hazard ratio (HR) of progression free survival (PFS) and overall survival (OS) in NSCLC patients with various NLR.Results: A total of 14 retrospective studies consisting of 1225 NSCLC patients were included. The combined results showed that relatively higher baseline NLR was associated with poor PFS (HR = 1.44; 95% confidence interval (CI):1.18–1.77; p < 0.05) and OS (HR = 1.75; 95% CI: 1.33–2.30; p < 0.05) after treatment of Nivolumab. Subgroup analysis suggested that NLR ≥ 5 was more reliable for PFS (HR = 1.73; 95%CI: 1.14, 2.62; p < 0.05) and OS (HR = 1.76; 95%CI: 1.47, 2.10; p < 0.05). In addition, post-treatment NLR also had predictive roles for PFS (HR = 3.17; 95%CI: 1.48, 6.82; p < 0.05) and OS (HR = 2.26; 95%CI: 1.05, 4.86; p < 0.05).Conclusion: Our findings suggest that NLR can be used as a prognostic biomarker for NSCLC treating with Nivolumab, and the recommended cutoff value of NLR is 5.

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Section: Combined Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A reliable and feasible way to predict the benefits of Nivolumab in patients with non-small cell lung cancer: a pooled analysis of 14 retrospective studies

Cao

et al. 2018

OncoImmunology

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“…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%

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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“…Patients were dichotomized according to prespecified cutoff values of NLR ≥3 (high NLR [H‐NLR]) versus <3 (low NLR [L‐NLR]) and PLR ≥180 (high PLR [H‐PLR]) versus <180 (low PLR [L‐PLR]) . The cutoffs were chosen according to literature references .…”

Section: Methodsmentioning

confidence: 99%

Peripheral Blood Markers Identify Risk of Immune-Related Toxicity in Advanced Non-Small Cell Lung Cancer Treated with Immune-Checkpoint Inhibitors

et al. 2019

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Background Immune‐checkpoint inhibitors (ICIs) are now standard of care for advanced non‐small cell lung cancer (NSCLC). Unfortunately, many patients experience immune‐related adverse events (irAEs), which are usually mild and reversible, but they require timely management and may be life threatening. No predictive markers of irAEs are available. Materials and Methods The neutrophil‐to‐lymphocyte ratio (NLR) and platelet‐to‐lymphocyte ratio (PLR) were evaluated in patients with NSCLC consecutively treated with ICIs. Prespecified cutoff values of NLR and PLR were used and related to outcome and onset of irAEs. A control group of patients with advanced NSCLC not receiving ICIs was included. Results The study included 184 patients: 26 (14.1%) received pembrolizumab upfront, and 142 (77%) received ICIs (pembrolizumab, nivolumab or atezolizumab) after one or more lines of chemotherapy. The median number of ICIs cycles was six (range, 1–61). The median progression‐free survival and overall survival were 4.8 (95% CI, 3.4–6.3) and 20.6 (95% CI, 14.7–26.5) months, respectively. Sixty patients (32.6%) developed irAEs, mainly grade 1–2 (65.0%), causing ICI interruption in 46 cases (25.0%). Low NLR and low PLR at baseline were significantly associated with the development of irAEs (odds ratio [OR], 2.2; p = .018 and OR, 2.8; p = .003, respectively). Multivariate analyses confirmed PLR as independent predictive marker of irAEs (OR, 2.3; p = .020). Conclusion NLR and PLR may predict the appearance of irAEs in non‐oncogene‐addicted aNSCLC, although this conclusion warrants prospective validation. Implications for Practice This study was designed to investigate the role of blood biomarkers in predicting the occurrence of immune‐related adverse events (irAEs) in patients with advanced non‐small cell lung cancer receiving immunotherapy. The results of the study suggest a potential predictive role of neutrophil‐to‐lymphocyte ratio and platelet‐to‐lymphocyte ratio as markers for irAE development in this category of patients. These data provide rationale for an easy and feasible application to be validated in clinical practice.

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Neutrophil-to-lymphocyte ratio as an early marker of outcomes in patients with advanced non-small-cell lung cancer treated with nivolumab

Cited by 110 publications

References 31 publications

A reliable and feasible way to predict the benefits of Nivolumab in patients with non-small cell lung cancer: a pooled analysis of 14 retrospective studies

A reliable and feasible way to predict the benefits of Nivolumab in patients with non-small cell lung cancer: a pooled analysis of 14 retrospective studies

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

Peripheral Blood Markers Identify Risk of Immune-Related Toxicity in Advanced Non-Small Cell Lung Cancer Treated with Immune-Checkpoint Inhibitors

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