Skip to main content

Research in Review

Dose Escalation of CML Treatment Improves Molecular Response Rates

August 02, 2017

Patients with chronic myeloid leukemia (CML) in the chronic phase may achieve molecular response with safe and effective treatment dose escalation, according to a recent study.


Related Content

CML Mutations Associated With Treatment Failure

NCCN Updates Treatment Guidelines for CML


Previous research has shown that dose escalation or reductions of the tyrosine kinase inhibitor nilotinib can be beneficial for some patients with CML. Further research is needed to assess dose adjustments for optimization purposes in this population.

Timothy P Hughes, MD, South Australian Health and Medical Research Institute, and colleagues conducted an open-label, prospective phase III study (ENESTxtnd) to evaluate molecular response to nilotinib in patients with newly diagnosed CML in the chronic phase and the impact of novel dose optimization on patient outcomes. A total of 421 patients from 18 countries were sampled and were allowed dose escalation of nilotinib (300 mg to 400 mg twice daily) in the case of suboptimal response or treatment failure, and dose re-escalation in those who required a reduction due to serious adverse events. Median time on treatment was 23.7 months.

Results of the study were published in the British Journal of Hematology (online July 12, 2017; doi: 10.1111/bjh.14829).

In total, 144 patients received a reduced dose of nilotinib during the study, 84 of whom received a dose re-escalation to a dose lower than prescribed. Among those with reduced doses, 106 patients attempted to re-escalate to 300 mg twice daily, 92 of whom did so successfully.

Eighty-eight patients escalated their nilotinib dose to 400 mg twice daily due to a lack of efficacy. Among these patients, 83 remained on the higher dose at the end of treatment.

Cumulative rate of major molecular response (MMR) after 12 months was 70.8%; after 24 months, the cumulative rate of MMR was 81%. Among the 144 patients with dose reductions, 109 (75.7%) achieved MMR by 24 months, including 84.8% of those who successfully re-escalated their dose. Among the 88 patients with escalated dosing, 56 (63.6%) achieved MMR by 24 months.

The safety profile of nilotinib was consistent with prior studies.

Authors of the study concluded that higher MMR rates were observed in their study compared with previous trials, which may be due to higher overall dose intensity. The study “demonstrate(s) the feasibility and potential benefits of nilotinib dose optimization,” they wrote.—Zachary Bessette

Back to Top