Effects of first- and second-generation tyrosine kinase inhibitor therapy on glucose and lipid metabolism in chronic myeloid leukemia patients: A real clinical problem?

Alessandra Iurlo, Emanuela Orsi, Daniele Cattaneo, Veronica Resi, Cristina Bucelli, Nicola Orofino, Mariarita Sciumè, Chiara Elena, Valeria Grancini, Dario Consonni, Ester Maria Orlandi, Agostino Cortelezzi

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Background: Tyrosine kinase inhibitors (TKIs) have dramatically changed the prognosis of patients with chronic myeloid leukemia (CML). They have a distinct toxicity profile that includes glycometabolic alterations: i.e. diabetes mellitus (DM), impaired fasting glucose (IFG), and the metabolic syndrome (MS). The aim of this study was to evaluate the prevalence of these alterations in a cohort of CML-chronic phase patients treated with imatinib, dasatinib or nilotinib. Methods: The study involved 168 consecutive CML-chronic phase patients with no history of DM/IFG or MS. Anthropometric and metabolic parameters were assessed, and DM/IFG and MS were diagnosed based on the criteria of the American Diabetes Association and the National Cholesterol Education Program-Adult Treatment Panel III, respectively. Results: The nilotinib group had significantly higher levels of fasting plasma glucose, insulin, C-peptide, insulin resistance, and total and LDL cholesterol than the imatinib and dasatinib groups. DM/IFG were identified in 25% of the imatiniband dasatinib-treated patients, and 33% of those in the nilotinib cohort (p = 0.39 vs imatinib and p = 0.69 vs dasatinib). A diagnosis of MS was made in 42.4% of the imatinib-treated patients, 37.5% of the dasatinib-treated patients, and 36.1% of the nilotinib-treated patients (p = 0.46 vs imatinib and p = 0.34 vs dasatinib). Conclusions: Treatment with nilotinib does not seem to induce DM/IFG or the MS to a significantly higher extent than imatinib or dasatinib, though it causes a worse glycometabolic profile. These findings suggest the need for a close monitoring of glucose and lipid metabolism and a multidisciplinary approach in patients treated with nilotinib.

Original languageEnglish
Pages (from-to)33944-33951
Number of pages8
JournalOncotarget
Volume6
Issue number32
DOIs
Publication statusPublished - 2015

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Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Lipid Metabolism
Protein-Tyrosine Kinases
Glucose
Fasting
Diabetes Mellitus
Leukemia, Myeloid, Chronic Phase
Therapeutics
C-Peptide
Dasatinib
LDL Cholesterol
Insulin Resistance
Imatinib Mesylate
4-methyl-N-(3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl)-3-((4-pyridin-3-ylpyrimidin-2-yl)amino)benzamide
Cholesterol
Insulin
Education

Keywords

  • Chronic myeloid leukemia
  • Dasatinib
  • Diabetes mellitus
  • Imatinib
  • Metabolic syndrome
  • Nilotinib

ASJC Scopus subject areas

  • Oncology

Cite this

Effects of first- and second-generation tyrosine kinase inhibitor therapy on glucose and lipid metabolism in chronic myeloid leukemia patients : A real clinical problem? / Iurlo, Alessandra; Orsi, Emanuela; Cattaneo, Daniele; Resi, Veronica; Bucelli, Cristina; Orofino, Nicola; Sciumè, Mariarita; Elena, Chiara; Grancini, Valeria; Consonni, Dario; Orlandi, Ester Maria; Cortelezzi, Agostino.

In: Oncotarget, Vol. 6, No. 32, 2015, p. 33944-33951.

Research output: Contribution to journalArticle

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title = "Effects of first- and second-generation tyrosine kinase inhibitor therapy on glucose and lipid metabolism in chronic myeloid leukemia patients: A real clinical problem?",
abstract = "Background: Tyrosine kinase inhibitors (TKIs) have dramatically changed the prognosis of patients with chronic myeloid leukemia (CML). They have a distinct toxicity profile that includes glycometabolic alterations: i.e. diabetes mellitus (DM), impaired fasting glucose (IFG), and the metabolic syndrome (MS). The aim of this study was to evaluate the prevalence of these alterations in a cohort of CML-chronic phase patients treated with imatinib, dasatinib or nilotinib. Methods: The study involved 168 consecutive CML-chronic phase patients with no history of DM/IFG or MS. Anthropometric and metabolic parameters were assessed, and DM/IFG and MS were diagnosed based on the criteria of the American Diabetes Association and the National Cholesterol Education Program-Adult Treatment Panel III, respectively. Results: The nilotinib group had significantly higher levels of fasting plasma glucose, insulin, C-peptide, insulin resistance, and total and LDL cholesterol than the imatinib and dasatinib groups. DM/IFG were identified in 25{\%} of the imatiniband dasatinib-treated patients, and 33{\%} of those in the nilotinib cohort (p = 0.39 vs imatinib and p = 0.69 vs dasatinib). A diagnosis of MS was made in 42.4{\%} of the imatinib-treated patients, 37.5{\%} of the dasatinib-treated patients, and 36.1{\%} of the nilotinib-treated patients (p = 0.46 vs imatinib and p = 0.34 vs dasatinib). Conclusions: Treatment with nilotinib does not seem to induce DM/IFG or the MS to a significantly higher extent than imatinib or dasatinib, though it causes a worse glycometabolic profile. These findings suggest the need for a close monitoring of glucose and lipid metabolism and a multidisciplinary approach in patients treated with nilotinib.",
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T1 - Effects of first- and second-generation tyrosine kinase inhibitor therapy on glucose and lipid metabolism in chronic myeloid leukemia patients

T2 - A real clinical problem?

AU - Iurlo, Alessandra

AU - Orsi, Emanuela

AU - Cattaneo, Daniele

AU - Resi, Veronica

AU - Bucelli, Cristina

AU - Orofino, Nicola

AU - Sciumè, Mariarita

AU - Elena, Chiara

AU - Grancini, Valeria

AU - Consonni, Dario

AU - Orlandi, Ester Maria

AU - Cortelezzi, Agostino

PY - 2015

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AB - Background: Tyrosine kinase inhibitors (TKIs) have dramatically changed the prognosis of patients with chronic myeloid leukemia (CML). They have a distinct toxicity profile that includes glycometabolic alterations: i.e. diabetes mellitus (DM), impaired fasting glucose (IFG), and the metabolic syndrome (MS). The aim of this study was to evaluate the prevalence of these alterations in a cohort of CML-chronic phase patients treated with imatinib, dasatinib or nilotinib. Methods: The study involved 168 consecutive CML-chronic phase patients with no history of DM/IFG or MS. Anthropometric and metabolic parameters were assessed, and DM/IFG and MS were diagnosed based on the criteria of the American Diabetes Association and the National Cholesterol Education Program-Adult Treatment Panel III, respectively. Results: The nilotinib group had significantly higher levels of fasting plasma glucose, insulin, C-peptide, insulin resistance, and total and LDL cholesterol than the imatinib and dasatinib groups. DM/IFG were identified in 25% of the imatiniband dasatinib-treated patients, and 33% of those in the nilotinib cohort (p = 0.39 vs imatinib and p = 0.69 vs dasatinib). A diagnosis of MS was made in 42.4% of the imatinib-treated patients, 37.5% of the dasatinib-treated patients, and 36.1% of the nilotinib-treated patients (p = 0.46 vs imatinib and p = 0.34 vs dasatinib). Conclusions: Treatment with nilotinib does not seem to induce DM/IFG or the MS to a significantly higher extent than imatinib or dasatinib, though it causes a worse glycometabolic profile. These findings suggest the need for a close monitoring of glucose and lipid metabolism and a multidisciplinary approach in patients treated with nilotinib.

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