Blood Predictive Biomarkers for Patients With Non-small-cell Lung Cancer Associated With Clinical Response to Nivolumab

In this study, several potential blood biomarkers have been evaluated as predictive of response to nivolumab monotherapy in a cohort of patients with non small-cell lung cancer. lactate dehydrogenase and interleukin-11 levels, neutrophils-to lymphocyte ratio, indoleamine 2,3 dioxygenase activity, and BCL-2 interacting mediator of cell death expression in CD8+ T cells were determined at baseline, after 2 months of treatment start, and at disease progression. High baseline lactate dehydrogenase level, increased interleukin-8 level, indoleamine 2,3 dioxygenase activity, or BCL-2 interacting mediator of cell death expression through the treatment could be predictors of response to anti-programmed cell death protein 1 therapy. Background: Immunotherapy is a promising cancer treatment, but surrogate biomarkers of clinical efficacy have not been fully validated. The aim of this work was to evaluate several biomarkers as predictors of response to nivolumab monotherapy in patients with non-small-cell lung cancer. Patients and Methods: Blood samples was collected at baseline, at 2 months after treatment start, and at disease progression. Lactate dehydrogenase level (LDH), neutrophils, and leukocyte values were obtained from medical record. Interleukin (IL)-8, IL-11, and kynurenine/tryptophan levels were determined by enzyme-linked immunosorbent assay. Total protein was extracted from circulating CD8+ T cells, and BCL-2 interacting mediator of cell death (BIM) protein expression tested by western blotting. Results: Baseline LDH levels were significantly higher in non-responder patients than in those who responded (P- .045). The increase in indoleamine 2,3 dioxygenase activity was related to progression of disease, mainly in patients who did not respond to nivolumab treatment (P - .001). Increased levels of circulating IL-8 were observed in initially responding patients at time of progression, and it was related to lower overall survival (hazard ratio, 7.49; P - .025). A highest expression of BIM in circulating CD8+ T cells could be related to clinical benefit. The Student t test and Mann-Whitney U test were used to compare groups for continuous variables. Time to events was estimated using the Kaplan-Meier method, and compared by the log-rank test. Conclusions: Changes in plasma LDH and IL-8, indoleamine 2,3 dioxygenase activity, and BIM expression in CD8+ T cells could be used to monitor and predict clinical benefit from nivolumab treatment in these patients. (C) 2019 Elsevier Inc. All rights reserved.