Patients with chronic myeloid leukemia (CML) who attempt to discontinue tyrosine kinase inhibitor (TKI) therapy for a second time after a first unsuccessful attempt have strong treatment-free remission rates, according to new research published in Cancer (online July 25, 2017; doi:10.1002/cncr.30885).
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Multiple recent studies have shown high proportions of patients with CML who receive treatment with TKIs and achieve a deep molecular response are able to discontinue therapy without any safety repercussions. Patients who experience a molecular relapse after discontinuation often are able to achieve rapid deep molecular response after TKI re-initiation. However, a second attempt at TKI discontinuation for such patients has yet to be studied.
A group of French researchers led by Laurence Legros, MD, PhD, department of hematology, Nice University Hospital, conducted a study (RE-STIM) to evaluate treatment-free remission in patients with CML who re-attempted TKI discontinuation after an unsuccessful first attempt. The observational, multicenter trials involved 70 patients who discontinued treatment for the second time and were re-introduced to treatment only after an observed loss of major molecular response.
Median follow-up was 38.3 months (range, 4.7-117 months). Forty-five patients (64.3%) lost a major molecular response after a median time off therapy of 5.3 months (range, 2-42 months).
Researchers reported treatment-free remission rates were 48% at 12 months (95% CI, 37.6%-61.5%), 42% at 24 months (95% CI, 31.5%-55.4%), and 35% at 36 months (95% CI, 24.4%-49.4%). After TKI re-initiation for those patients with a relapse, no progression toward advanced-phase CML occurred and no efficacy issue was observed.
Univariate analysis revealed the speed of molecular relapse after the first TKI discontinuation attempt to be the only factor associated with outcomes after re-initiation. The treatment-free remission rate at 24 months was 72% (95% CI, 48.8%-100%) in patients who remained in deep molecular response within 3 months after the first TKI discontinuation and 36% (95% CI, 25.8%-51.3%) for all others.
Researchers concluded that this study “is the first to demonstrate that a second TKI discontinuation attempt is safe and that a first failed attempt at discontinuing TKI does not preclude a second successful attempt.”—Zachary Bessette
