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 1,2 , Emanuela Orsi 3 , Daniele Cattaneo 1 , Veronica Resi 3 , Cristina Bucelli 1 , Nicola Orofino 1 , Mariarita Sciumè 1 , Chiara Elena 4 , Valeria Grancini 3 , Dario Consonni 5 , Ester Maria Orlandi 4 and Agostino Cortelezzi 1 1 Oncohematology Division, IRCCS Ca’ Granda – Maggiore Policlinico Hospital Foundation, and University of Milan, Milan, Italy 2 Oncohematology Unit of the Elderly, IRCCS Ca’ Granda – Maggiore Policlinico Hospital Foundation, and University of Milan, Milan, Italy 3 Endocrinology and Diabetes Unit, Department of Medical Sciences, IRCCS Ca’ Granda – Maggiore Policlinico Hospital Foundation, and University of Milan, Milan, Italy 4 Oncology-Hematology Department, Hematology Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy 5 Epidemiology Unit, Department of Preventive Medicine, IRCCS Ca’ Granda – Maggiore Policlinico Hospital Foundation, Milan, Italy Correspondence to: Alessandra Iurlo, email: // Keywords : chronic myeloid leukemia, imatinib, dasatinib, nilotinib, diabetes mellitus, metabolic syndrome Received : June 18, 2015 Accepted : August 21, 2015 Published : September 10, 2015 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 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). 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.