Neutrophil-lymphocyte ratio kinetics in patients with advanced solid tumours on phase I trials of PD-1/PD-L1 inhibitors.
Eur J Cancer
; 89: 56-63, 2018 01.
Article
em En
| MEDLINE
| ID: mdl-29227818
ABSTRACT
BACKGROUND:
Although the neutrophil-lymphocyte ratio (NLR) is prognostic in many oncological settings, its significance in the immunotherapy era is unknown. Mechanistically, PD-1/PD-L1 inhibitors may alter NLR. We sought to characterise NLR kinetics in patients with advanced solid tumours treated with PD-1/PD-L1 inhibitors.METHODS:
Electronic records of patients treated with PD-1/PD-L1 inhibitors on phase I trials across three sites were reviewed. A high NLR (hNLR) was predefined as >5. Univariate logistic regression models were used for toxicity, response analyses and Cox models for overall survival (OS) and progression-free survival analyses. Landmark analyses were performed (cycle two, three). Longitudinal analysis of NLR was performed utilising a mixed effect regression model.RESULTS:
The median OS for patients with hNLR was 8.5 months and 19.4 for patients with low NLR, (hazard ratio [HR] = 1.85, 95% confidence interval [CI] 1.15-2.96, p = 0.01). On landmark analysis, hNLR was significantly associated with inferior OS at all time points with a similar magnitude of effect over time (p < 0.05). On multivariate analysis, NLR was associated with OS (HR 1.06, 95% CI 1.01-1.11, p = 0.01). NLR did not correlate with increased immune toxicity. Longitudinally, NLR correlated with response NLR decreased by 0.09 (95% CI -0.15 to -0.02; p = 0.01) per month in responders compared with non-responders.CONCLUSIONS:
hNLR at baseline and during treatment is adversely prognostic in patients with advanced malignancies receiving PD-1/PD-L1 blockade. Importantly, NLR reduced over time in responders to immunotherapy. Taken together, these data suggest that baseline and longitudinal NLR may have utility as a unique biomarker to aid clinical decision-making in patients receiving immunotherapy.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Linfócitos
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Antígeno B7-H1
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Receptor de Morte Celular Programada 1
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Neoplasias
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Neutrófilos
Tipo de estudo:
Clinical_trials
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Prognostic_studies
Limite:
Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article