Neutrophil-lymphocyte ratio kinetics in patients with advanced solid tumours on phase I trials of PD-1/PD-L1 inhibitors

Publication date: January 2018
Source:European Journal of Cancer, Volume 89
Author(s): Malaka Ameratunga, Maxime Chénard-Poirier, Irene Moreno Candilejo, Manuel Pedregal, Andrew Lui, David Dolling, Caterina Aversa, Alvaro Ingles Garces, Joo Ern Ang, Udai Banerji, Stan Kaye, Hui Gan, Bernard Doger, Victor Moreno, Johann de Bono, Juanita Lopez
BackgroundAlthough 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.MethodsElectronic 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.ResultsThe 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.ConclusionshNLR 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.



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