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

• Published in: Oncotarget 2015-10, Vol.6 (32), p.33944-33951
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Anthropometry; Blood Glucose - analysis; C-Peptide - blood; Clinical Research Paper; Cohort Studies; Dasatinib - therapeutic use; Female; Glucose - metabolism; Humans; Imatinib Mesylate - therapeutic use; Insulin - blood; Insulin Resistance; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - metabolism; Lipid Metabolism - drug effects; Male; Middle Aged; Protein Kinase Inhibitors - adverse effects; Protein Kinase Inhibitors - therapeutic use; Protein-Tyrosine Kinases - antagonists & inhibitors; Pyrimidines - therapeutic use; Young Adult
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.5580

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. 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. 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 imatinib- and 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). 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.