Abstract
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 μg/mL, 22.3 μg/mL and 27.1 μg/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 <18.7 μg/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.
Highlights
Immunotherapy represents the most revolutionary treatment for solid cancers nowadays.To date, several types of immunotherapy are available, including monoclonal antibodies, non-specific immunotherapies, oncolytic virus therapy, T-cell therapy and cancer vaccines
The evolution of immune checkpoint inhibitors as anticancer treatment options represents one of the most successful approaches in cancer drug research in the past few years [1]. Checkpoint inhibitor antibodies, such as anti-programmed cell death protein 1 (PD-1) and its ligand (PD-L1), are new drugs acting as tumor suppressing factors since they are able to modulate the interaction between the immune cell and the tumor cell [2]
Tests were performed using IBM SPSS Statistics 25.0 for Windows (Chicago, IL, USA). This is the first study showing an association between Vitamin D (VD)-related biomarkers and nivolumab plasma concentrations
Summary
Immunotherapy represents the most revolutionary treatment for solid cancers nowadays.To date, several types of immunotherapy are available, including monoclonal antibodies, non-specific immunotherapies, oncolytic virus therapy, T-cell therapy and cancer vaccines. The evolution of immune checkpoint inhibitors as anticancer treatment options represents one of the most successful approaches in cancer drug research in the past few years [1] Checkpoint inhibitor antibodies, such as anti-programmed cell death protein 1 (PD-1) and its ligand (PD-L1), are new drugs acting as tumor suppressing factors since they are able to modulate the interaction between the immune cell and the tumor cell [2]. These therapies proved to be a safe and effective option in advanced non-small cell lung cancer (NSCLC) and can be recommended selectively [3]. 272 patients treated with nivolumab had an overall survival of 3.2 months longer than those on docetaxel [2]
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