Importance of TKI treatment duration in treatment-free remission of chronic myeloid leukemia: results of the D-FREE study

Int J Hematol. 2023 May;117(5):694-705. doi: 10.1007/s12185-023-03549-3. Epub 2023 Feb 4.


Treatment-free remission (TFR) is a new goal for patients with chronic myeloid leukemia in chronic phase (CML-CP) with a sustained deep molecular response (DMR) to treatment with tyrosine kinase inhibitors (TKIs). However, optimal conditions for successful TFR in patients treated with second-generation (2G)-TKIs are not fully defined. In this D-FREE study, treatment discontinuation was attempted in newly diagnosed CML-CP patients treated with the 2G-TKI dasatinib who achieved BCR-ABL1 levels of ≤ 0.0032% (MR4.5) on the international scale (BCR-ABL1IS) and maintained these levels for exactly 1 year. Of the 173 patients who received dasatinib induction therapy for up to 2 years, 123 completed and 60 (48.8%) reached MR 4.5. Among the first 21 patients who maintained MR4.5 for 1 year and discontinued dasatinib, 17 experienced molecular relapse defined as loss of major molecular response (BCR-ABL1IS > 0.1%) confirmed once, or loss of MR4 (BCR-ABL1IS > 0.01%) confirmed on 2 consecutive assessments. The estimated molecular relapse-free survival rate was 16.7% at 12 months. This study was prematurely terminated according to the protocol's safety monitoring criteria. The conclusion was that sustained DMR for just 1 year is insufficient for TFR in CML-CP patients receiving dasatinib for less than a total of 3 years of treatment.

Keywords: Chronic myeloid leukemia; Dasatinib; Treatment-free remission.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents* / therapeutic use
  • Dasatinib / therapeutic use
  • Duration of Therapy*
  • Female
  • Humans
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive*
  • Male
  • Middle Aged
  • Remission Induction
  • Tyrosine Kinase Inhibitors* / therapeutic use
  • Young Adult


  • Tyrosine Kinase Inhibitors
  • Dasatinib
  • Antineoplastic Agents