The effect of nilotinib on major molecular responses (MMR) compared with imatinib in Japanese patients (pts) with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP): Results from the Japanese subset of ENESTnd.

Abstract

e17001 Background: Initial data from the global ENESTnd (Evaluating Nilotinib Efficacy and Safety in Clinical Trials-Newly Diagnosed Patients) trial demonstrated superior efficacy of nilotinib compared with imatinib in pts with newly diagnosed Ph+ CML-CP. The purpose of this post-hoc sub-group analysis was to assess the efficacy of nilotinib compared to imatinib in the subset of Japanese patients in ENESTnd. Methods: 79 (9%) Japanese pts of 846 total pts were randomized to nilotinib 300 mg twice a day (bid) (n = 30), nilotinib 400 mg bid (n = 24), or imatinib 400 mg once a day (qd) (n = 25). Primary endpoint was rate of MMR at 12 months (mo). Results: Baseline demographics were similar to the overall study population with the exception that there were fewer Japanese pts with high Sokal risk scores (10%, 13%, and 8% for nilotinib 300 mg bid, 400 mg bid, and imatinib) compared with the overall study population (28% across arms). Median dose intensities of nilotinib were near planned dosing in all treatment arms and similar to the overall population. Rates of MMR at 12 mo were at least twice as high for nilotinib 300 mg bid (57%) and 400 mg bid (50%) compared with imatinib (24%). Kaplan-Meier estimated median time to MMR was faster for nilotinib 300 mg bid (5.8 mo) and 400 mg bid (8.4 mo) compared with imatinib (not yet reached). Rates of complete cytogenetic response (CCyR) by 12 mo were similar for all treatment arms (nilotinib 300 mg bid, 77%; 400 mg bid, 83%; imatinib, 76%). No pts on nilotinib progressed, while 1 pt progressed on imatinib. Both drugs were well-tolerated. Conclusions: Nilotinib at both doses led to twice the rate of MMR in Japanese CML pts compared with imatinib. These data suggest that MMR is a more suitable endpoint compared to CCyR for measuring deeper responses to nilotinib, regardless of Sokal risk. Molecular responses at 12 mo were higher in the Japanese subset compared with the overall ENESTnd population. The improved efficacy of nilotinib compared with imatinib support the use of nilotinib in the treatment of Japanese patients with newly diagnosed Ph+ CML- CP. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis