Imatinib-resistant Philadelphia chromosome-positive (Ph-positive) leukemias could be treated using dasatinib

10-20-2006

According to recent research from the United States, "The BCR-ABL tyrosine kinase inhibitor imatinib is effective in Ph-positive leukemias, but relapse occurs, mainly as a result of the outgrowth of leukemic subclones with imatinib-resistant BCR-ABL mutations. We evaluated dasatinib, a BCR-ABL inhibitor that targets most imatinib-resistant BCR-ABL mutations, in patients with chronic myelogenous leukemia (CML) or Ph-positive acute lymphoblastic leukemia (ALL)."

"Patients with various phases of CML or with Ph-positive ALL who could not tolerate or were resistant to imatinib were enrolled in a phase 1 dose-escalation study," explained M. Talpaz and colleagues, University of California, Los Angeles. "Dasatinib (15 to 240 mg per day) was administered orally in four-week treatment cycles, once or twice daily. A complete hematologic response was achieved in 37 of 40 patients with chronic-phase CML, and major hematologic responses were seen in 31 of 44 patients with accelerated-phase CML, CML with blast crisis, or Ph-positive ALL

"In these two phases, the rates of major cytogenetic response were 45% and 25%, respectively. Responses were maintained in 95% of patients with chronic-phase disease and in 82% of patients with accelerated-phase disease, with a median follow-up more than 12 months and 5 months, respectively. Nearly all patients with lymphoid blast crisis and Ph-positive ALL had a relapse within 6 months. Responses occurred among all BCR-ABL genotypes, with the exception of the T315I mutation, which confers resistance to both dasatinib and imatinib in vitro."

The researchers concluded, "Myelosuppression was common but not dose-limiting. Dasatinib induces hematologic and cytogenetic responses in patients with CML or Ph-positive ALL who cannot tolerate or are resistant to imatinib."

Talpaz and colleagues published their study in New England Journal of Medicine (Dasatinib in imatinib-resistant Philadelphia chromosome-positive leukemias. N Engl J Med, 2006;354(24):2531-2541).

For additional information, contact C.L. Sawyers, University of California Los Angeles, Jonsson Comprehensive Cancer Center, 11-934 Factor Bldg, 10833 LeConte Avenue, Los Angeles, CA 90095, USA.

Publisher contact information for the New England Journal of Medicine is: Massachusetts Medical Society, Waltham Woods Center, 860 Winter St., Waltham, MA 02451-1413, USA.