Dasatinib induces complete hematologic and cytogenetic responses in patients with imatinib-resistant or -intolerant chronic myeloid leukemia in blast crisis

Jorge Cortes, Philippe Rousselot, Dong Wook Kim, Ellen Ritchie, Nelson Hamerschlak, Steven Coutre, Andreas Hochhaus, Francois Guilhot, Giuseppe Saglio, Jane Apperley, Oliver Ottmann, Neil Shah, Philipp Erben, Susan Branford, Prasheen Agarwal, Ashwin Gollerkeri, Michele Baccarani

Research output: Contribution to journalArticle

365 Scopus citations

Abstract

The prognosis for patients with chronic myeloid leukemia (CML) in myeloid blast crisis (MBC) or lymphoid blast crisis (LBC) remains poor. Although imatinib can induce responses in a subset of these patients, resistance to the drug develops rapidly. Dasatinib is a novel, oral, multitargeted kinase inhibitor of BCR-ABL and SRC family kinases. After promising phase 1 results, we report the results of phase 2 clinical trials of dasatinib in patients with imatinib-resistant or -intolerant blast crisis CML (MBC, n = 74; LBC, n = 42). At the 8-month follow-up, dasatinib induced major hematologic responses (MaHRs) in 34% and 31% of MBC- and LBC-CML patients and major cytogenetic responses (MCyRs) in 31% and 50% of these patients, respectively. Most (86%) of these MCyRs were complete cytogenetic responses (CCyRs). Responses were rapid and durable: 88% and 46%, respectively, of MBC- and LBC-CML patients achieving MaHR had not experienced disease progression at the 8-month follow-up. Response rates were similar in patients with and without BCR-ABL mutations known to confer resistance to imatinib. Dasatinib was well tolerated. Nonhematologic adverse events were mild to moderate. Cytopenias were common and could be managed by dose modification. Dasatinib is highly active and produces hematologic and cytogenetic responses in a significant number of patients with imatinib-resistant or -intolerant MBC- and LBC-CML. These trials were registered at www.clinicaltrials.gov as #CA180006 and #CA180015.

Original languageEnglish (US)
Pages (from-to)3207-3213
Number of pages7
JournalBlood
Volume109
Issue number8
DOIs
StatePublished - Apr 15 2007
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Cortes, J., Rousselot, P., Kim, D. W., Ritchie, E., Hamerschlak, N., Coutre, S., Hochhaus, A., Guilhot, F., Saglio, G., Apperley, J., Ottmann, O., Shah, N., Erben, P., Branford, S., Agarwal, P., Gollerkeri, A., & Baccarani, M. (2007). Dasatinib induces complete hematologic and cytogenetic responses in patients with imatinib-resistant or -intolerant chronic myeloid leukemia in blast crisis. Blood, 109(8), 3207-3213. https://doi.org/10.1182/blood-2006-09-046888