Vitamin D plasma level can affect nivolumab drug exposure in a cohort of patients with non-small-cell lung cancer

Introduction: immune-checkpoint inhibition using programmed cell death-1 and its ligand drug inhibitors have improved survival, among patients with advanced non-small-cell lung cancer (NSCLC): nivolumab is one of the last approved. Vitamin D deficiency (<20 ng/mL) is frequent in lung cancer patients and studies showed this pre-hormone modulates the expression of genes involved in drug pathway and in the immune system regulation. Furthermore, not many biomarkers related to nivolumab therapy are present in literature. The aim of this study was to understand which factors were able to predict nivolumab concentrations and its anti-antibody levels in patients’ plasma at 15, 45 and 60 days of therapy. Methods: forty-five patients with advanced NSCLC were enrolled to receive nivolumab. Enzyme-linked immunosorbent assay was used for drug and vitamin D quantification. Results: Median nivolumab plasma levels were 12.5, 22.3 and 27.1 µg/mL respectively at 15, 45 and 60 days (p<0.001). No anti-nivolumab antibodies have been detected. 25-hydroxyvitamin D median concentrations were 12.8 ng/mL at baseline, 13.6 ng/mL at 15 days, 11.8 ng/mL at 45 days and 12.9 ng/mL at 60 days. Gender significantly affected nivolumab concentrations (p=0.010 at 15 days, p=0.033 at 45 days and p=0.006 at 60 days). In linear regression analyses, 25-hydroxyvitamin D <20 ng/mL before starting therapy, gender and 25-hydroxyvitamin D <20 ng/mL at 15 days were able to predict nivolumab concentrations respectively at 15, 45 and 60 days of treatment. Conclusions: for the first time, this study shows factors able to predict nivolumab exposure at different timings, but further, studies in bigger and different cohorts are needed to clarify these data.