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

Research output: Contribution to journalArticle

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

Fingerprint

Vitamin D
Non-Small Cell Lung Carcinoma
Single Nucleotide Polymorphism
Anti-Idiotypic Antibodies
nivolumab
Therapeutics
Genes
Real-Time Polymerase Chain Reaction
Immune System
Enzyme-Linked Immunosorbent Assay
Genotype
Monoclonal Antibodies
Gene Expression
Pharmaceutical Preparations

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., ... 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

Influence of Vitamin D in advanced non-small cell lung cancer patients treated with nivolumab. / Cusato, Jessica; Genova, Carlo; Tomasello, Cristina; Carrega, Paolo; Ottonello, Selene; Pietra, Gabriella; Mingari, Maria Cristina; Cossu, Irene; Rijavec, Erika; Leggieri, Anna; Di Perri, Giovanni; Dal Bello, Maria Giovanna; Coco, Simona; Boccardo, Simona; Ferlazzo, Guido; Grossi, Francesco; D’Avolio, Antonio.

In: Cancers, Vol. 11, No. 1, 125, 01.01.2019.

Research output: Contribution to journalArticle

Cusato, J, Genova, C, Tomasello, C, Carrega, P, Ottonello, S, Pietra, G, Mingari, MC, Cossu, I, Rijavec, E, Leggieri, A, Di Perri, G, Dal Bello, MG, 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, vol. 11, no. 1, 125. https://doi.org/10.3390/cancers11010125
Cusato, Jessica ; Genova, Carlo ; Tomasello, Cristina ; Carrega, Paolo ; Ottonello, Selene ; Pietra, Gabriella ; Mingari, Maria Cristina ; Cossu, Irene ; Rijavec, Erika ; Leggieri, Anna ; Di Perri, Giovanni ; Dal Bello, Maria Giovanna ; Coco, Simona ; Boccardo, Simona ; Ferlazzo, Guido ; Grossi, Francesco ; D’Avolio, Antonio. / Influence of Vitamin D in advanced non-small cell lung cancer patients treated with nivolumab. In: Cancers. 2019 ; Vol. 11, No. 1.
@article{17826b13eaaf44d68d1d6a3388aa9493,
title = "Influence of Vitamin D in advanced non-small cell lung cancer patients treated with nivolumab",
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.",
keywords = "ELISA, Immunotherapy, Monoclonal antibody, NSCLC, Pharmacogenetics, Pharmacokinetics",
author = "Jessica Cusato and Carlo Genova and Cristina Tomasello and Paolo Carrega and Selene Ottonello and Gabriella Pietra and Mingari, {Maria Cristina} and Irene Cossu and Erika Rijavec and Anna Leggieri and {Di Perri}, Giovanni and {Dal Bello}, {Maria Giovanna} and Simona Coco and Simona Boccardo and Guido Ferlazzo and Francesco Grossi and Antonio D’Avolio",
year = "2019",
month = "1",
day = "1",
doi = "10.3390/cancers11010125",
language = "English",
volume = "11",
journal = "Cancers",
issn = "2072-6694",
publisher = "MDPI AG",
number = "1",

}

TY - JOUR

T1 - Influence of Vitamin D in advanced non-small cell lung cancer patients treated with nivolumab

AU - Cusato, Jessica

AU - Genova, Carlo

AU - Tomasello, Cristina

AU - Carrega, Paolo

AU - Ottonello, Selene

AU - Pietra, Gabriella

AU - Mingari, Maria Cristina

AU - Cossu, Irene

AU - Rijavec, Erika

AU - Leggieri, Anna

AU - Di Perri, Giovanni

AU - Dal Bello, Maria Giovanna

AU - Coco, Simona

AU - Boccardo, Simona

AU - Ferlazzo, Guido

AU - Grossi, Francesco

AU - D’Avolio, Antonio

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

KW - ELISA

KW - Immunotherapy

KW - Monoclonal antibody

KW - NSCLC

KW - Pharmacogenetics

KW - Pharmacokinetics

UR - http://www.scopus.com/inward/record.url?scp=85061983133&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85061983133&partnerID=8YFLogxK

U2 - 10.3390/cancers11010125

DO - 10.3390/cancers11010125

M3 - Article

VL - 11

JO - Cancers

JF - Cancers

SN - 2072-6694

IS - 1

M1 - 125

ER -