Rapid reduction in BCR-ABL1 transcript predicts deep molecular response in dasatinib-treated chronic-phase chronic myeloid leukaemia patients

Eur J Haematol. 2018 Jan;100(1):27-35. doi: 10.1111/ejh.12969. Epub 2017 Oct 16.

Abstract

Objectives: We conducted a phase-II study to evaluate the efficacy and safety of dasatinib in patients newly diagnosed with chronic-phase chronic myeloid leukaemia (CML-CP) in Japan (IMIDAS PART 2 study).

Methods: Seventy-nine patients were administered 100 mg dasatinib once daily. We examined pretreatment and post-treatment influences of various factors. The BCR-ABL1 international scale (IS), halving time (HT) and reduction rate of BCR-ABL1 transcript within the initial 1 or 3 months of therapy (RR-BCR-ABL11m,3m ) were the post-treatment factors investigated to predict the molecular response.

Results: The estimated major molecular response (MMR), molecular response 4.0 (MR4.0) and molecular response 4.5 (MR4.5) rates were 77.2%, 49.4% and 35.4%, respectively, at 12 months. Grade 3/4 non-haematologic adverse events were infrequent. Multivariate analysis showed that age >65 years was significantly correlated with MR4.0 and MR4.5 (deep molecular response: DMR) at 12 months. All post-treatment factors at 3 months predicted DMR by univariate analysis. However, RR-BCR-ABL13m was the only significant landmark for predicting DMR by multivariate analysis.

Conclusions: Primary treatment of CML-CP with dasatinib enabled early achievement of MMR and DMR, particularly in elderly patients, with high safety. Furthermore, RR-BCR-ABL13m was found to be a more useful predictor of DMR than HT-BCR-ABL1 and BCR-ABL1 IS.

Keywords: chronic myeloid leukaemia; deep molecular response; tyrosine kinase inhibitors.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Dasatinib / administration & dosage
  • Dasatinib / adverse effects
  • Dasatinib / therapeutic use*
  • Female
  • Fusion Proteins, bcr-abl / genetics*
  • Gene Expression*
  • Humans
  • Leukemia, Myeloid, Chronic-Phase / diagnosis
  • Leukemia, Myeloid, Chronic-Phase / drug therapy*
  • Leukemia, Myeloid, Chronic-Phase / genetics*
  • Male
  • Middle Aged
  • Prognosis
  • Proportional Hazards Models
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use*
  • Time Factors
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Fusion Proteins, bcr-abl
  • Dasatinib