Nilotinib dose-optimization in newly diagnosed chronic myeloid leukaemia in chronic phase: final results from ENESTxtnd

作者：Hughes Timothy P^*; Munhoz Eduardo; Salvino Marco Aurelio; Ong Tee Chuan; Elhaddad Alaa; Shortt Jake; Quach Hang; Pavlovsky Carolina; Louw Vernon J; Shih Lee Yung; Turkina Anna G; Meillon Luis; Jin Yu; Acharya Sandip; Dalal Darshan; Lipton Jeffrey H

来源：British Journal of Haematology, 2017, 179(2): 219-228.

DOI：10.1111/bjh.14829

• chronic myeloid leukaemia
• tyrosine kinase inhibitor
• nilotinib
• molecular response
• dose optimization

The Evaluating Nilotinib Efficacy and Safety in Clinical Trials-Extending Molecular Responses (ENESTxtnd) study was conducted to evaluate the kinetics of molecular response to nilotinib in patients with newly diagnosed chronic myeloid leukaemia in chronic phase and the impact of novel dose-optimization strategies on patient outcomes. The ENESTxtnd protocol allowed nilotinib dose escalation (from 300 to 400mg twice daily) in the case of suboptimal response or treatment failure as well as dose re-escalation for patients with nilotinib dose reductions due to adverse events. Among 421 patients enrolled in ENESTxtnd, 70.8% (95% confidence interval, 66.2-75.1%) achieved major molecular response (BCR-ABL10.1% on the International Scale) by 12months (primary endpoint). By 24months, 81.0% of patients achieved major molecular response, including 63.6% (56 of 88) of those with dose escalations for lack of efficacy and 74.3% (55 of 74) of those with dose reductions due to adverse events (including 43 of 54 patients with successful re-escalation). The safety profile of nilotinib was consistent with prior studies. The most common non-haematological adverse events were headache, rash, and nausea; cardiovascular events were reported in 4.5% of patients (grade 3/4, 3.1%). The study was registered at clinicaltrials.gov (NCT01254188).

• 出版日期2017-10
• 单位长春大学