Final 3-year Results of the Dasatinib Discontinuation Trial in Patients With Chronic Myeloid Leukemia Who Received Dasatinib as a Second-line Treatment

DADI Trial Group, Japan

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42 Citations (Scopus)

Abstract

We describe the results of a prospective trial of the discontinuation of second-line dasatinib treatment in chronic myeloid leukemia patients who maintained a deep molecular response for > 1 year. The treatment-free remission rate at 36 months was 44.4%. High natural killer cell counts before discontinuation correlated significantly with successful therapy discontinuation. Introduction: We previously reported an interim analysis of the DADI (dasatinib discontinuation) trial. The results showed that 48% of patients with chronic myeloid leukemia in the chronic phase who maintained a deep molecular response (DMR) for ≥ 1 year could discontinue second- or subsequent-line dasatinib treatment safely at a median follow-up of 20 months. However, the results from longer follow-up periods would be much more useful from a clinical perspective. Patients and Methods: The DADI trial was a prospective, multicenter trial conducted in Japan. After confirming a stable DMR for ≥ 1 year, dasatinib treatment subsequent to imatinib or nilotinib was discontinued. After discontinuation, the loss of DMR (even of 1 point) was defined as stringent molecular relapse, thereby triggering therapy resumption. The predictive factors of treatment-free remission (TFR) were analyzed. Results: The median follow-up period was 44.0 months (interquartile range, 40.5-48.0 months). The estimated overall TFR rate at 36 months was 44.4% (95% confidence interval, 32.0%-56.2%). Only 2 patients developed a molecular relapse after the 1-year cutoff point. The presence of imatinib resistance was a significant risk factor for molecular relapse. Moreover, high natural killer cell and low γδ+ T-cell and CD4+ regulatory T-cell (CD25+CD127low) counts before discontinuation correlated significantly with successful therapy discontinuation. Conclusion: These findings suggest that discontinuation of second- or subsequent-line dasatinib after a sustained DMR of ≥ 1 year is feasible, especially for patients with no history of imatinib resistance. In addition, the natural killer cell count was associated with the TFR.

Original languageEnglish
Pages (from-to)353-360.e1
JournalClinical Lymphoma, Myeloma and Leukemia
Volume18
Issue number5
DOIs
Publication statusPublished - 2018 May

Keywords

  • CML
  • DADI
  • Natural killer cell
  • Stop trial
  • Treatment-free remission

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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