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

Abstract 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 non-small cell lung cancer patients. Patients and Methods Blood samples was collected at baseline, at two months after treatment start, and to disease progression. LDH, neutrophils, and leukocytes values were obtained from medical record. IL-8, IL-11, and kynurenine/tryptophan levels were determined by ELISA. Total protein was extracted from circulating CD8+ T cells, and BIM protein expression tested by western blotting. Results Baseline LDH levels were significantly higher in non-responder patients than in those who responded (P= 0.045). The increase in IDO activity was related to progression disease, mainly in patients who did not respond to Nivolumab treatment (P= 0.001). Increased levels of circulating IL-8 were observed in initially responding patients at time of progression, and it was related to lower overall survival (HR= 7.49; P= 0.025). A highest expression of BIM in circulating CD8+ T cells could be related to clinical benefit. Student’s 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, IDO activity, and BIM expression in CD8+ T cells could be used to monitor and predict clinical benefit from Nivolumab treatment in these patients.