Malaka Ameratunga1, Maxime Chénard-Poirier2, Irene Moreno Candilejo3, Manuel Pedregal4, Andrew Lui5, David Dolling6, Caterina Aversa1, Alvaro Ingles Garces1, Joo Ern Ang1, Udai Banerji1, Stan Kaye1, Hui Gan7, Bernard Doger4, Victor Moreno4, Johann de Bono1, Juanita Lopez8. 1. The Drug Development Unit, Institute of Cancer Research and the Royal Marsden Hospital, Downs Road, Sutton, UK. 2. The Drug Development Unit, Institute of Cancer Research and the Royal Marsden Hospital, Downs Road, Sutton, UK; CHU de Québec - Université Laval, Quebec City, Canada. 3. The Drug Development Unit, Institute of Cancer Research and the Royal Marsden Hospital, Downs Road, Sutton, UK; START Madrid-FJD, Hospital Fundación Jiménez Díaz, Madrid, Spain. 4. START Madrid-FJD, Hospital Fundación Jiménez Díaz, Madrid, Spain. 5. Austin Health and Olivia Newton-John Cancer Research Institute, Melbourne, Australia. 6. Clinical Trials and Statistics Unit, Institute of Cancer Research, Sutton, UK. 7. Austin Health and Olivia Newton-John Cancer Research Institute, Melbourne, Australia; La Trobe University School of Cancer Medicine, Melbourne, Australia; Department of Medicine, University of Melbourne, 145 Studley Road, Heidelberg, Victoria 3084, Australia. 8. The Drug Development Unit, Institute of Cancer Research and the Royal Marsden Hospital, Downs Road, Sutton, UK. Electronic address: Juanita.lopez@icr.ac.uk.
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.
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: Donald T Weed; Serena Zilio; Isildinha M Reis; Zoukaa Sargi; Marianne Abouyared; Carmen R Gomez-Fernandez; Francisco J Civantos; Carla P Rodriguez; Paolo Serafini Journal: Front Immunol Date: 2019-05-31 Impact factor: 7.561
Authors: Mingjia Li; Daniel Spakowicz; Jarred Burkart; Sandip Patel; Marium Husain; Kai He; Erin M Bertino; Peter G Shields; David P Carbone; Claire F Verschraegen; Carolyn J Presley; Gregory A Otterson; Kari Kendra; Dwight H Owen Journal: J Cancer Res Clin Oncol Date: 2019-07-31 Impact factor: 4.553
Authors: D Viñal; L Gutierrez-Sainz; D Martinez; J A Garcia-Cuesta; J Pedregosa; J Villamayor; L Ostios; D Sanchez-Cabrero; O Higuera; A Pinto; N Rodriguez-Salas; E Espinosa; J de Castro; J Feliu Journal: Clin Transl Oncol Date: 2020-11-23 Impact factor: 3.405