Tyrosine kinase inhibitors (TKIs) discontinuation in patients with Philadelphia-chromosome-positive chronic myeloid leukemia (Ph-positive CML) is increasingly considered. We aim to evaluate the outcome of patients with CML who discontinued TKIs, and determine the factors associated with differences in the success rates of treatment-free remission (TFR). Patients with Ph-positive CML treated between October 1999 and February 2017 who discontinued therapy were analyzed. A major molecular response (MMR) was defined as BCR-ABL1/ABL1 ratio on the International Scale ≤0.1%. TFR failure was defined as the loss of MMR on any single test. We analyzed TFR rates according to duration and depth of response, and conducted a multivariate analysis for factors associated with loss of MMR. Two-hundred and eighty-four patients were analyzed; 199 patients (70%) electively discontinued TKIs. At a median follow-up of 36 months (95% confidence interval, 32–40) after TKI discontinuation, 53 patients (19%) lost MMR. The estimated 5-year TFR rate was 79%. All but one patient regained MMR after resuming therapy. The estimated 5-year TFR rates were higher with MR4 and MR4.5 ≥5 years, compared with MR4 <5 years (87% vs. 92% vs. 64%; p <.0001). By multivariate analysis, only the duration of MR4 or MR4.5 ≥5 years before stopping treatment was associated with a lower risk of loss of MMR. In summary, TFR is safe and feasible in patients with Ph-positive CML on TKI therapy. Achieving MR4 or MR4.5 for at least 5 years is correlated with a better outcome.
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