Baseline neutrophil-to-lymphocyte ratio (NLR) and derived NLR could predict overall survival in patients with advanced melanoma treated with nivolumab

Capone, Mariaelena; Giannarelli, Diana; Mallardo, Domenico; Madonna, Gabriele; Festino, Lucia; Grimaldi, Antonio; Vanella, Vito; Simeone, Ester; Paone, Miriam; Palmieri, Giuseppe; Cavalcanti, Ernesta; Caracò, Corrado; Ascierto, Paolo A.

doi:10.1186/s40425-018-0383-1

Cited by 325 publications

(327 citation statements)

References 30 publications

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“…Our findings directly corroborate those of a recent study by Capone et al examining the outcomes of 97 patients treated with nivolumab stratified by NLR . In that study, which used the same NLR cutoff, a very similar proportion of patients (approximately 25%) demonstrated an elevated baseline NLR, and the baseline NLR was highly prognostic for both OS and PFS.…”

Section: Discussionsupporting

confidence: 89%

“…These findings are consistent with other studies of the NLR in the setting of checkpoint inhibition, which find that an elevated baseline NLR alone does not appear to have sufficient prognostic magnitude to merit withholding PD-1 inhibitor therapy. 14,16,17,19,31 Rather, an elevated NLR may identify a patient population of particular interest for clinical trials testing PD-1 inhibition in combination with additional agents. Our findings directly corroborate those of a recent study by Capone et al examining the outcomes of 97 patients treated with nivolumab stratified by NLR.…”

Section: Discussionmentioning

confidence: 99%

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High neutrophil‐to‐lymphocyte ratio (NLR) is associated with treatment failure and death in patients who have melanoma treated with PD‐1 inhibitor monotherapy

Bartlett

Flynn

Panageas

et al. 2019

Cancer

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Background An elevated neutrophil‐to‐lymphocyte ratio (NLR) is associated with poor survival in patients with cancer, including those who receive immunotherapies. The authors sought to investigate NLR as a biomarker of treatment outcomes in patients with melanoma who were treated with PD‐1 inhibition. Methods Patients undergoing initial treatment with PD‐1 inhibitor monotherapy for stage IV melanoma at a single center from 2012 to 2015 were included. Clinical characteristics and the NLR at baseline and before subsequent treatment cycles were collected. The time to treatment failure (TTF) and overall survival (OS) were evaluated using Kaplan‐Meier and landmark analyses. Results Among 224 study patients, 63 (28%) had a baseline NLR ≥5. The baseline NLR was significantly associated with Eastern Cooperative Oncology Group performance status and the number of involved metastatic sites. With a median follow‐up of 39 months in survivors, a baseline NLR ≥5 was independently associated with shorter OS (hazard ratio, 2.0; 95% CI, 1.3‐2.9) and TTF (hazard ratio, 1.7; 95% CI, 1.2‐2.4). An NLR increase ≥30% during the first 2 cycles of treatment was associated with worse OS (median, 47 vs 13.5 months; P < .001) and a trend toward shorter TTF (12.8 vs 5.9 months; P = .05). A combined baseline NLR ≥5 and an NLR increase ≥30% identified a small cohort with markedly shortened OS (median, 5.8 months) and TTF (median, 1.8 months). Conclusions Elevated baseline NLR and an increased NLR early during treatment are prognostic for TTF and OS in patients who have melanoma treated with PD‐1 inhibitor monotherapy. Combined, these biomarkers can widely risk‐stratify patients for treatment failure and survival.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

High neutrophil‐to‐lymphocyte ratio (NLR) is associated with treatment failure and death in patients who have melanoma treated with PD‐1 inhibitor monotherapy

Bartlett

Flynn

Panageas

et al. 2019

Cancer

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“…To date, some factors that correlate with clinical response to anti-PD-1 agents have been identified. A number of bloodderived factors including high relative eosinophil count and relative lymphocyte count, low dNLR, low LDH and absence of metastasis other than soft-tissue/lung have been associated with better OS in melanoma patients treated with anti-PD-1 agents [33,34], as observed here. In addition, high mutational burden in human tumors, including melanoma, correlates with clinical response to PD-1 inhibitors [35].…”

Section: Discussionsupporting

confidence: 71%

“…Low neutrophil-to-lymphocyte ratio (NLR) and low derived NLR (dNLR) resulted also significantly associated with OS in patients treated with nivolumab ( Table 2 and Additional file 2: Fig. S2), accordingly to our recently published data [34]. Focusing on CD8+ cells subsets, CD8+PD-1+ lymphocytes < 9.8% median frequency (p < 0.009) and CD8+PD-1+CD73+ lymphocytes < 2.3% median frequency (p < 0.001) were significantly associated with OS, whilst the proportion of CD8+T cells positive only to CD73 resulted no significantly associated with OS ( Table 2).…”

Section: Association Of Pre-treatment Cd8+cd73+t Cells Frequency Withsupporting

confidence: 80%

Frequency of circulating CD8+CD73+T cells is associated with survival in nivolumab-treated melanoma patients

et al. 2020

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Background: PD-1 blocking agents, such as nivolumab, have demonstrated clear anti-tumor effects and clinical benefits in a subset of patients with advanced malignancies. Nonetheless, more efforts are needed to identify reliable biomarkers for outcome, to correctly select patients who will benefit from anti-PD-1 treatment. The aim of this study was to investigate the role of peripheral CD8+T cells expressing CD73, involved in the generation of the immune suppressive molecule adenosine, in predicting outcome after nivolumab treatment in advanced melanoma patients. Methods:PBMCs from 100 melanoma patients treated with nivolumab were collected at National Cancer Institute "G. Pascale" of Naples. Frequencies of CD8+ lymphocytes phenotypes were assessed by flow cytometry at baseline before nivolumab treatment, along with clinical characteristics and blood count parameters. Healthy controls (n = 20) were also analysed. Percentages of baseline T cells expressing PD-1 and CD73 were correlated with outcome after nivolumab treatment.Results: Melanoma patients presented a lower frequency of total circulating CD8+ lymphocytes than control subjects (p = 0.008). Patients with low baseline percentage of circulating CD8+PD-1+CD73+ lymphocytes (< 2.3%) had better survival (22.4 months vs 6.9 months, p = 0.001). Patients (39%) with clinical benefit from nivolumab therapy presented a significantly lower frequency of circulating CD8+PD-1+CD73+ lymphocytes than patients who progressed to nivolumab treatment (p = 0.02). Conclusions:Our observations suggest that baseline CD73 expression on circulating CD8+PD-1+ lymphocytes appear a promising biomarker of response to anti-PD-1 treatment in melanoma patients. Further investigations are needed for validation and for clarifying its role as prognostic or predictive marker.

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“…According to previous published work, we selected 3, 4, 5 and 4.7 (the median) as the NLR cut-off values. [16][17][18] There was not any significant difference between those values and OS (Table S2b). In this study, we confirmed that NLR at baseline, prior to ipilimumab, was not associated with OS after first sequential ipilimumab administration.…”

Section: Immune Cell Measurements Before and During Treatmentmentioning

confidence: 99%

Investigation of clinical factors associated with longer overall survival in advanced melanoma patients treated with sequential ipilimumab

Muto¹,

Kitano

Tsutsumida

et al. 2019

The Journal of Dermatology

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Melanoma is one of the most serious form of skin cancer. Nowadays, ipilimumab is used for advanced melanoma refractory to first‐line anti‐programmed death 1 (PD‐1) antibodies. Thirty patients (male : female ratio, 18:12; median age, 60.5 years) sequentially treated with ipilimumab after anti‐PD‐1 antibody (nivolumab or pembrolizumab), while 58 (male : female ratio, 27:31; median age, 66.5 years) with anti‐PD‐1 antibody only. The kind of therapy and schedules were as follows: nivolumab, 2 mg/kg at 3‐week intervals or at 3 mg/kg every 2 week; pembrolizumab, 2 mg/kg every 3 weeks; ipilimumab, 3 mg/kg at 3‐week intervals for four doses. The sequential therapy was selected for the patients with disease progression and/or recovered from severe (immune‐related [ir]) adverse events (AE) after PD‐1 blockade monotherapy. We evaluated multiple parameters and analyzed their relevance to overall survival (OS). The best objective response rate was 6.7% in sequential ipilimumab treatment. Median OS was 163 days (range, 16–489). Baseline absolute lymphocyte count (ALC) and performance status (PS) before sequential ipilimumab were associated with OS in univariate analyses. Baseline PS and irAE within 6 weeks after ipilimumab administration showed significant differences on multivariate analysis. Prior to first‐line PD‐1 blockade, these parameters were not associated with OS. The other factors (i.e. age, sex, number of doses, absolute neutrophil counts, neutrophil : lymphocyte ratio, lactate dehydrogenase and C‐reactive protein) were not associated with OS. [Correction added on 17 April 2019, after first online publication: ‘not related to OS' has been amended to ‘not associated with OS’.] Ipilimumab as sequential therapy did not appear to improve OS and was associated with more severe irAE than PD‐1 blockade monotherapy. We need to carefully consider treating patients with poor PS and low ALC.

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Baseline neutrophil-to-lymphocyte ratio (NLR) and derived NLR could predict overall survival in patients with advanced melanoma treated with nivolumab

Cited by 325 publications

References 30 publications

High neutrophil‐to‐lymphocyte ratio (NLR) is associated with treatment failure and death in patients who have melanoma treated with PD‐1 inhibitor monotherapy

High neutrophil‐to‐lymphocyte ratio (NLR) is associated with treatment failure and death in patients who have melanoma treated with PD‐1 inhibitor monotherapy

Frequency of circulating CD8+CD73+T cells is associated with survival in nivolumab-treated melanoma patients

Investigation of clinical factors associated with longer overall survival in advanced melanoma patients treated with sequential ipilimumab

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