Clinical Efficacy and Safety of First-Line Dasatinib Therapy and the Relevance of Velocity of BCR-ABL1 Transcript Decline for Achievement of Molecular Responses in Newly Diagnosed Chronic-Phase Chronic Myeloid Leukemia: Report from the Juntendo Yamanashi Cooperative Study Group

Oncology. 2018;94(2):85-91. doi: 10.1159/000481945. Epub 2017 Nov 18.

Abstract

Objective: The use of tyrosine kinase inhibitors led to an improvement in the prognoses of patients with chronic myeloid leukemia (CML). The aims of this study were to investigate the efficacy and safety of dasatinib in Japanese patients and to explore the factors that affect the achievement of molecular responses.

Methods: The primary endpoint was a major molecular response (MMR) by 12 months. The halving time for BCR-ABL1 transcripts was calculated using transcript levels.

Results: Thirty-two patients with chronic-phase CML (CML-CP) were enrolled and 30 received 100 mg dasatinib once daily. At 24 months of follow-up, 21 (72%) and 24 (83%) patients achieved an MMR by 12 and 24 months, respectively; the rates of a deep molecular response (DMR) by 12 and 24 months were 48 and 59%, respectively. A shorter halving time of BCR-ABL1 transcripts (≤10.6 days) accurately predicted both an MMR and a DMR. The incidence of pleural effusion was 50%. Our study reconfirmed the efficacy and safety of dasatinib treatment in Japanese patients with newly diagnosed CML-CP. In addition, the usefulness of the halving time of BCR-ABL1 transcripts was validated.

Conclusion: These data emphasize the significance of an early treatment response in achieving a DMR during dasatinib therapy.

Keywords: Dasatinib; Halving time; Lymphocytosis; Molecular response; Newly diagnosed chronic myeloid leukemia.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / therapeutic use*
  • Dasatinib / therapeutic use*
  • Female
  • Fusion Proteins, bcr-abl / genetics*
  • Humans
  • Japan
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics
  • Leukemia, Myeloid, Chronic-Phase / drug therapy*
  • Leukemia, Myeloid, Chronic-Phase / genetics
  • Male
  • Middle Aged
  • Prognosis
  • Prospective Studies
  • Protein Kinase Inhibitors / therapeutic use*

Substances

  • Antineoplastic Agents
  • BCR-ABL1 fusion protein, human
  • Protein Kinase Inhibitors
  • Fusion Proteins, bcr-abl
  • Dasatinib