Safety and Efficacy of Frontline Nilotinib (Nb) for Chronic Phase (CP) Chronic Myeloid Leukemia (CML) in Diabetic Patients (pts)

Nilotinib is accepted standard of care for CP-CML as initial therapy or after resistance or intolerance to imatinib. Nilotinib increases blood sugar level in diabetic and non-diabetic patients. This has caused concern about the possible adverse consequences for diabetic pts treated with nilotinib. Purpose: To investigate the impact that nilotinib therapy may have over diabetes among pts with CML receiving frontline therapy for CML. Methods: We reviewed the records of 105 CML patients treated at our institution from 7/2005 to 7/2011 who have received treatment with nilotinib 400 mg twice daily as a frontline for their CML disease. We divided our patient in two groups (Diabetes =DM- vs. non-Diabetes =non-DM-). For diabetic patients, we identified the concomitant mediations at the time of DM, DM-associated complications, occurrence of hyperglycemia during nilotinib therapy and the management of DM during their therapy with nilotinib. We compare the best and current response on nilotinib, event-free survival (EFS), treatment- free survival (TFS), and overall survival (OS) between the two groups (DM vs. non-DM). Results: The median age for the 105 pts treated was 52 yrs (range, 17 to 89), and 63 were males (60%). Nine patients (9%) were diabetic. Three of the 9 DM pts had DM complications before starting nilotinib (vitreous hemorrhage, proliferative diabetic retinopathy, and neuropathy). Median BMI was 26.9 (19.2 to 40.2) Kg/m2and 35.6(31.3 to 38.2) Kg/m2 in non-DM and DM pts respectively. Dose reductions to 400 mg or 200 mg were required in 24 non-DM pts (23 %) compared with 3 DM pts (3%). Hyperglycemia was not identified as the reason for reducing nilotinib doses in any DM pt. The median blood sugar at the start of therapy with nilotinib was 93 mg/dL (65 to167) and 123 mg/dL (64 to 329) in non-DM and DM pts respectively. The median peak blood sugar during the treatment with nilotinib was 126 mg/dL (84 to 196) in non-DM pts and 251 mg/dL (158 to 299) in DM pts. The blood sugar of two DM pts (22%) was controlled by diet without the need of using any diabetic medications and 7 pts (78%) received different kinds of oral hypoglycemia medications (biguanides, sulfonylureas, thiazolidinediones, alpha-glucosidase inhibitors, and meglitinides) before starting Nilotinib. During nilotinib therapy 1 of these 7 pts (11%) was converted to insulin due to inability to control blood sugar by using oral hypoglycemia medications 1 (11%) did not require change in DM management, and 5 pts (56%) required an increase in the dose of their DM medication or addition of other oral hypoglycemia medications. Nilotinib was not interrupted because of hyperglycemia in any pt. None of DM pts developed ketoacidosis or hyperosmolar coma. The outcome of CML for DM and non-DM pts is presented in table 1. Conclusion: Nilotinib is a safe and active medication in CML patients with DM. Close monitoring and adequate management of DM allows DM pts with CML to safely receive therapy with nilotinib and derive equal benefits as their non-DM counterparts.

Cortes:Deciphera: Research Funding; Pfizer: Consultancy, Research Funding; Ariad: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Novartis: Consultancy, Research Funding.