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Title: Neutrophil-lymphocyte ratio kinetics in patients with advanced solid tumours on phase I trials of PD-1/PD-L1 inhibitors.
Austin Authors: Ameratunga, Malaka;Chénard-Poirier, Maxime;Moreno Candilejo, Irene;Pedregal, Manuel;Lui, Andrew;Dolling, David;Aversa, Caterina;Ingles Garces, Alvaro;Ang, Joo Ern;Banerji, Udai;Kaye, Stan;Gan, Hui K ;Doger, Bernard;Moreno, Victor;de Bono, Johann;Lopez, Juanita
Affiliation: The Drug Development Unit, Institute of Cancer Research and the Royal Marsden Hospital, Downs Road, Sutton, UK
La Trobe University School of Cancer Medicine, Melbourne, Australia
Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia
CHU de Québec - Université Laval, Quebec City, Canada
START Madrid-FJD, Hospital Fundación Jiménez Díaz, Madrid, Spain
Austin Health, Heidelberg, Victoria, Australia
Clinical Trials and Statistics Unit, Institute of Cancer Research, Sutton, UK
Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
Issue Date: Jan-2018
Date: 2017-12-08
Publication information: European journal of cancer (Oxford, England : 1990) 2018; 89: 56-63
Abstract: 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. 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. 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. 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.
DOI: 10.1016/j.ejca.2017.11.012
Journal: European journal of cancer (Oxford, England : 1990)
PubMed URL: 29227818
Type: Journal Article
Subjects: Neutrophil-lymphocyte ratio
PD-1 inhibitors
Phase I trials
Appears in Collections:Journal articles

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