Influence of Vitamin D in advanced non-small cell lung cancer patients treated with nivolumab

Jessica Cusato, Carlo Genova, Cristina Tomasello, Paolo Carrega, Selene Ottonello, Gabriella Pietra, Maria Cristina Mingari, Irene Cossu, Erika Rijavec, Anna Leggieri, Giovanni Di Perri, Maria Giovanna Dal Bello, Simona Coco, Simona Boccardo, Guido Ferlazzo, Francesco Grossi, Antonio D’Avolio

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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.

Original languageEnglish
Article number125
JournalCancers
Volume11
Issue number1
DOIs
Publication statusPublished - Jan 1 2019

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Keywords

  • ELISA
  • Immunotherapy
  • Monoclonal antibody
  • NSCLC
  • Pharmacogenetics
  • Pharmacokinetics

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Cusato, J., Genova, C., Tomasello, C., Carrega, P., Ottonello, S., Pietra, G., Mingari, M. C., Cossu, I., Rijavec, E., Leggieri, A., Di Perri, G., Dal Bello, M. G., Coco, S., Boccardo, S., Ferlazzo, G., Grossi, F., & D’Avolio, A. (2019). Influence of Vitamin D in advanced non-small cell lung cancer patients treated with nivolumab. Cancers, 11(1), [125]. https://doi.org/10.3390/cancers11010125