Dasatinib-associated major molecular responses in patients with chronic myeloid leukemia in chronic phase following imatinib failure: Response dynamics and predictive value

A. Hochhaus, M. C. Müller, J. Radich, S. Branford, H. M. Kantarjian, B. Hanfstein, P. Rousselot, D. W. Kim, J. H. Lipton, E. Bleickardt, A. Lambert, T. P. Hughes

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30 Citations (Scopus)

Abstract

Dasatinib is a highly potent BCR-ABL inhibitor that has shown durable efficacy in patients with chronic phase (CP) chronic myeloid leukemia (CML) after resistance, suboptimal response, or intolerance to prior imatinib. In patients with CML, BCR-ABL transcript measurement is the most sensitive method for assessing minimal residual disease. Here, molecular responses were analyzed in 1067 patients with CML-CP treated with dasatinib during phase II/III trials. After 3, 6, 12, and 24 months of follow-up, a major molecular response (MMR) was achieved by 12, 22, 35, and 40% of patients, respectively. The 24-month MMR rate was 34% in patients with resistance or suboptimal response to imatinib (n=829) and 63% in imatinib-intolerant patients (n=238). Among patients who had achieved a complete cytogenetic response (CCyR), 72% also achieved MMR. Responses with dasatinib 100mg once daily were similar to other doses. In landmark analyses, 24-month progressionfree survival was higher in patients who had achieved MMR or CCyR at 12 months than in those without MMR or CCyR at 12 months. MMR at 12 months was associated with a longer duration of CCyR. Overall, this analysis shows that dasatinib treatment results in high MMR rates in patients with CML-CP after imatinib failure.

Original languageEnglish
Pages (from-to)1628-1633
Number of pages6
JournalLeukemia
Volume23
Issue number9
DOIs
Publication statusPublished - 1 Sep 2009

Keywords

  • BCR-ABL
  • Chronic myeloid leukemia
  • Dasatinib
  • Progression-free survival
  • Treatment outcome

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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