Nivolumab is one of the most commonly used
monoclonal antibodies for advanced
non-small cell lung cancer treatment, to the extent that the presence of its anti-antibody is considered a negative prognostic factor.
Vitamin D (VD) modulates expression of the genes involved in drug metabolism and elimination. Immune system regulation and immunodeficiency is frequent in
non-small cell lung cancer patients. To date, no data have been reported about the relationship between
nivolumab and VD. The aim of this study was to quantify plasma 25-hydroxyVD (25-VD) and 1,25-VD,
nivolumab, and its anti-antibody before starting treatment (baseline) and at 15, 45 and 60 days of
therapy. VD-pathway-associated gene single nucleotide polymorphisms (SNPs) were also evaluated. Molecules were quantified through
enzyme-linked
immunosorbent assay, and SNPs through real-time PCR. Forty-five patients were enrolled. Median
nivolumab concentrations were 12.5 ug/mL, 22.3 ug/mL and 27.1 ug/mL at 15, 45 and 60 days respectively. No anti-
nivolumab antibodies were found. Correlations were observed between
nivolumab concentrations and 25-VD levels.
Nivolumab concentrations were affected by VD-pathway-related gene SNPs. VDBP AC/CC genotype and baseline 25-VD < 10 ng/mL predicted a
nivolumab concentration cut-off value of <18.7ug/mL at 15 days, which was associated with
tumor progression. This is the first study showing VD marker predictors of
nivolumab concentrations in a real-life context of
non-small cell lung cancer treatment.