Hospitalizations of Patients with Newly Diagnosed CML-CP Treated with Nilotinib or Imatinib: Results From a Randomized Phase III Trial

Abstract 3826

Background: Imatinib is the current standard of care for chronic myelogenous leukemia (CML). Nilotinib is a highly potent and the most selective inhibitor of BCR-ABL. A Phase III multi-center, open label, randomized study (ENESTnd) was conducted comparing these two therapies in adult patients with newly diagnosed Philadelphia Chromosome positive (Ph+) CML in chronic phase. The primary endpoint analysis at 12 months demonstrated that major molecular response (MMR) was significantly improved with nilotinib 300 mg BID (44%) and nilotinib 400 mg BID (43%) compared to imatinib 400 mg QD (22%; p < 0.001). The discontinuation rate due to adverse events was lowest among the nilotinib 300mg BID treatment arm (5%) compared to 7% in the imatinib arm, and nilotinib 400 mg BID (9%). Based on the results of this clinical trial, nilotinib 300 mg BID was approved for initial use for CML-CP in the US.

Aim: To evaluate the occurrence and rate of hospitalizations and time away from usual activities in this phase III trial.

Methods: A total of 846 patients were randomized to receive nilotinib 300 mg BID (n=282), nilotinib 400 mg BID (n=281) or imatinib 400mg QD (n=283). Hospitalizations, defined as any visit to the hospital requiring an overnight stay, excluding pre-planned or elective surgery, were assessed throughout the study period. Overdispersed Poisson regression models were used to compare the days hospitalized per 1,000 patient-days on study. Patients were asked to report time-off, defined as average number of hours per week taken away from all usual activities due to CML and side effects of CML treatment over the past 4 weeks, at Baseline and at the end of Months 3 and 12. The Wilcoxon rank-sum test was used to compare the time off from usual activities at each assessment; and t-tests were used to evaluate the within-group changes in time off.

Results: There were a total of 57 hospitalizations in the imatinib arm versus 48 hospitalizations in the nilotinib 300 mg BID arm, and 74 hospitalizations in the nilotinib 400 mg BID arm (Table). Descriptive statistics for length of stay (LOS) are presented in the Table. The hospitalization rate, expressed as hospital days per 1,000 patient days, was 47% higher in the imatinib arm compared to the nilotinib 300 mg BID arm (p=0.057) and 8% higher compared to the nilotinib 400 mg BID arm (p=0.68). Patients in the nilotinib 300mg BID arm had fewer stays and shorter LOS than the imatinib arm, whereas patients in the nilotinib 400mg BID arm had more stays than the imatinib arm but shorter LOS on average resulting in fewer total hospital days. The majority of hospitalizations (56%) in all three arms occurred within the first 9 months. Time off from usual activities, which began at an average level of 8–10 hours per week at Baseline, decreased in each arm, but the decrease did not significantly differ between arms (Table). Similar results were observed when patients reporting zero hours of time off were excluded from the analysis. There was no association between time off and age.

Summary/conclusions: In patients with newly diagnosed CML-CP, nilotinib resulted in less hospital time compared to imatinib, although this difference did not reach statistical significance. Additionally, patients in all three treatment groups reported significant improvements from baseline in time off from usual activities.