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

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.

authors

  • Ameratunga, Malaka
  • Chenard-Poirier, Maxime
  • Moreno Candilejo, Irene
  • Pedregal, Manuel
  • Lui, Andrew
  • Dolling, David
  • Aversa, Caterina
  • Garces, Alvaro Ingles
  • Ang, Joo Ern
  • Banerji, Udai
  • Kaye, Stan
  • Gan, Hui
  • Doger, Bernard
  • Moreno, Victor
  • de Bono, Johann
  • Lopez, Juanita

publication date

  • 2018