CLINICAL TRIALS AND OBSERVATIONS Brief report

Developing strategies to counteract ima-tinib resistance constitutes a challenge in chronic myelogenous leukemia (CML). Therapy with the tyrosine kinase inhibitors nilotinib (AMN107) and dasatinib (BMS-354825) has produced high rates of hemato-logic and cytogenetic response. Src kinase activation has been linked to Bcr-Abl–medi-ated leukemogenesis and CML progres-sion. In addition to binding Abl kinase with less stringent conformational requirements than imatinib, dasatinib is a potent Src ki-nase inhibitor. In the current study, we re-port on 23 patients with CML (19 of them in accelerated or blastic phases) treated with dasatinib after treatment failure with both imatinib and nilotinib. More than half (13; 57%) of 23 patients responded to dasatinib: 10 (43%) had a complete hematologic re-sponse (CHR), including 7 (30%) who had a cytogenetic response (2 complete, 4 partial, and 1 minor). These results suggest that dasatinib may be active in some patients after failure with both imatinib and nilotinib