Hochhaus A et al. (2007) Dasatinib induces notable hematologic and cytogenetic responses in chronic-phase chronic myeloid leukemia after failure of imatinib therapy. Blood 109: 2303–2309

Imatinib is widely used in the treatment of chronic myeloid leukemia (CML), a disorder characterized by the presence of the BCR-ABL fusion gene; however, the therapeutic options for patients with imatinib-resistant or imatinib-intolerant chronic-phase CML (CML-CP) are limited. A recent phase II study showed that dasatinib, a novel oral agent active against BCR-ABL, induce remarkable responses in patients with CML-CP resistant or intolerant to imatinib.

The study included 186 patients with CML-CP who received a median dasatinib dose of 101 mg/day for a median duration of 8.3 months. After therapy, complete hematologic responses were noted in 90% of patients. In imatinib-resistant and imatinib-intolerant patients, complete hematologic response rates were 87% and 97%, respectively. Major cytogenetic responses were noted in 52% of patients, with 50 of 127 patients being imatinib-resistant and 47 of 59 patients being imatinib-intolerant. Responses with dasatinib were sustained in 96% of imatinib-resistant and 100% of imatinib-intolerant patients. The progression-free survival rate was 92.4% and responses were observed across all BCR-ABL genotypes, even in patients with BCR-ABL mutations conferring imatinib resistance. Dasatinib was generally well tolerated; only 9% of patients discontinued treatment because of adverse effects. Cytopenias were the most common hematologic adverse effects. Nonhematologic events due to dasatinib were generally reversible and included headache, fatigue and dyspnea (grade 1 or 2); however, 3% of patients experienced pleural effusions (grade 3 to 4).

This study demonstrates that dasatinib is an effective and well-tolerated agent for the treatment of patients with CML-CP resistant or intolerant to imatinib.