Nilotinib Safe, Effective in Patients With Chronic-Phase Chronic Myeloid Leukemia and Type 2 Diabetes

ORLANDO, Fla.Hyperglycemia occurring during front-line treatment with nilotinib was usually mild, transient, manageable, and did not lead to treatment discontinuation in patients with chronic-phase chronic myeloid leukemia (CML-CP) with or without preexisting type 2 diabetes.

That's the conclusion of a prospective analysis to determine nilotinib effects on glucose metabolism in a subset of patients from the randomized, multicenter, phase 3 study, ENESTnd (Evaluating Nilotinib Efficacy and Safety in Clinical Trials of Newly Diagnosed Philadelphia chromosome-positive CML pts) trial, noted Giuseppe Saglio, MD, PhD, of the University of Turin, Orbassano, Italy, and colleagues. The analysis also found efficacy and safety of nilotinib in this subset of patients with type 2 diabetes to be similar to the overall population in ENESTnd.

Results from ENESTnd found nilotinib demonstrated superior efficacy, including significantly lower rates of progression on treatment to the accelerated or blastic phases of CML vs imatinib. However, previous reports had indicated that in some patients who received second-line nilotinib 400 mg bid for resistance or intolerance to imatinib, nilotinib may have led to transient hyperglycemia.

In this analysis, changes from baseline in glucose metabolism parameters, including fasting blood glucose (FBG), insulin, C-peptide, and A1C levels at 12 months, were assessed in the subset of patients with diabetes. Changes in body weight were also assessed.

The safety analysis of ENESTnd (n=836) included 279 patients in the nilotinib 300 mg bid arm, 277 in the nilotinib 400 mg bid arm, and 280 in the imatinib arm. Median follow-up was 18 months. In this population, all grade hyperglycemia occurred in 38% of patients in the nilotinib 300 mg bid arm, 42% of those in the 400 mg bid nilotinib arm, and 22% in the imatinib arm. Grade 3/4 hyperglycemia was 6%, 4%, and 0% for each of the groups, respectively. No patient from any treatment arm discontinued the study due to hyperglycemia, and there were no diabetic serious adverse events (eg, diabetic ketoacidosis, hyperosmolar events, and/or hospitalization due to diabetes).

The subset of patients with preexisting type 2 diabetes (n=57; 23 in the nilotinib 300 mg bid arm; 18 in the nilotinib 400 mg bid arm, and 16 pts in the imatinib arm) was analyzed for glucose metabolism parameters and efficacy. Median age was higher (~60 years) compared with the entire patient population (~47 years). At study entry, 39 of the 57 patients (68%) were on diabetes medications; 7 of the 39 (18%) were on insulin. The majority of patients with diabetes (74%) did not have a change in diabetes therapy on study. Changes in glucose metabolism parameters were minimal (Table 1). Please click here for more study data. No meaningful changes in body weight or A1C were noted in any arm.

Response rates in the subset of patients with preexisting type 2 diabetes were similar to the overall population: by 12 months, major molecular response (MMR) rates were 69.6% in the nilotinib 300 mg bid arm; 55.6% in the nilotinib 400 mg bid arm; and 25% in the imatinib arm, and CCyR rates were 69.6%, 77.8%, and 68.8%, respectively. No patient in the diabetic subset had progressed to advanced disease.

Overall, 8, 5, and 6 patients with diabetes discontinued nilotinib 300 mg bid, nilotinib 400 mg bid, and imatinib, respectively. Of these, 3, 5, and 4 patients discontinued due to an adverse event or laboratory abnormality unrelated to diabetes. One patient with diabetes in each of the nilotinib arms experienced an ischemic heart disease event (grade 1 or 2). Two patients with diabetes died, 1 due to intestinal obstruction and 1 due to suicide, both in the nilotinib 300 mg bid arm.