Dasatinib in the treatment of chronic myeloid leukemia in accelerated phase after imatinib failure: the START a trial

J Clin Oncol. 2009 Jul 20;27(21):3472-9. doi: 10.1200/JCO.2007.14.3339. Epub 2009 Jun 1.

Abstract

PURPOSE Patients with chronic myelogenous leukemia in accelerated phase (CML-AP) that is resistant or intolerant to imatinib have limited therapeutic options. Dasatinib, a potent inhibitor of BCR-ABL and SRC-family kinases, has efficacy in patients with CML-AP who have experienced treatment failure with imatinib. We now report follow-up data from the full patient cohort of 174 patients enrolled onto a phase II trial to provide a more complete assessment of the efficacy and safety of dasatinib in this population. PATIENTS AND METHODS Patients with imatinib-resistant (n = 161) or -intolerant (n = 13) CML-AP received dasatinib 70 mg orally twice daily. Results At a median follow-up of 14.1 months (treatment duration, 0.1 to 21.7 months), major and complete hematologic responses were attained by 64% and 45% of patients, respectively, and major and complete cytogenetic responses were achieved in 39% and 32% of patients, respectively. Responses were achieved irrespective of imatinib status (resistant or intolerant), prior stem-cell transplantation, or the presence of prior BCR-ABL mutation. The 12-month progression-free survival and overall survival rates were 66% and 82%, respectively. Dasatinib was generally well tolerated; the most frequent nonhematologic severe treatment-related adverse event was diarrhea (52%; grade 3 to 4, 8%). Cytopenias were common, including grade 3 to 4 neutropenia (76%) and thrombocytopenia (82%). Pleural effusion occurred in 27% of patients (grade 3 to 4, 5%). CONCLUSION Dasatinib is effective in patients with CML-AP after imatinib treatment failure.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Benzamides
  • Dasatinib
  • Disease-Free Survival
  • Female
  • Humans
  • Imatinib Mesylate
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Male
  • Middle Aged
  • Piperazines / therapeutic use*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Pyrimidines / therapeutic use*
  • Thiazoles / therapeutic use*
  • Treatment Failure*
  • Treatment Outcome
  • Young Adult

Substances

  • Benzamides
  • Piperazines
  • Pyrimidines
  • Thiazoles
  • Imatinib Mesylate
  • Dasatinib