Discontinuation of Nilotinib Feasible for Chronic Phase CML With Sustained MMR

CHICAGO-More than half of patients with chronic myeloid leukemia (CML) in the chronic phase who achieved a deep molecular response (MR) after a minimum of 3 years’ treatment with the tyrosine kinase inhibitor (TKI) nilotinib were able to maintain treatment-free remission, according to the results of the ENESTFreedom study.

“The treatment-free remission rate observed in this trial is clinically meaningful considering the relatively short duration of nilotinib therapy,” said study presenter Andreas Hochhaus, MD, of Jena University Hospital in Germany, during his presentation of the results (abstract 7001) at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 3–7 in Chicago.

Patients with chronic phase disease who had 2 or more years of front-line nilotinib and MR^4.5 (BCR-ABL1^IS ≤ 0.0032%) were eligible for the trial. The researchers enrolled 215 patients and continued their nilotinib for 1 year with RQ-PCR assessments every 12 weeks (consolidation phase). Patients with no assessment worse than MR⁴, two or fewer assessments between MR⁴ (BCR-ABL1^IS ≤ 0.001%) and MR^4.5, and MR^4.5in the last assessment were eligible to stop therapy. Any patient who lost major molecular response (MMR) re-initiated nilotinib.

Of the 215 patients enrolled, 190 patients stopped nilotinib and entered the treatment-free remission phase. The median duration of treatment was 3.6 years. At week 48, 51.6% (95% CI, 44.2%–58.9%) of the 190 patients were still in MMR and did not need to re-initiate therapy.

Hochhaus noted that the trial did not meet its primary objective, the percentage of patients in MMR at 48 weeks in the treatment-free remission phase, per the original statistical assumption that the lower limit of the 95% CI will be equal to or greater than 50%.

Eighty-six patients had to re-initiate treatment with nilotinib due to loss of MMR, but 98.8% were able to regain MMR and 88.4% achieved MR^4.5.

In his discussion of the results, Richard A. Larson, MD, of the University of Chicago, listed some of the reasons why these patients may wish to discontinue treatment with nilotinib. For many patients, he said, taking nilotinib is a daily reminder that they have CML. Young women with the disease may wish to stop the drug for a planned pregnancy, and patients may wish to avoid the high costs associated with continual treatment with these drugs.

Based on these results, Larson said, it appears that “some patients with CML in deep molecular remission can remain treatment-free after discontinuation of TKI therapy.”