Dasatinib Early Intervention After Cytogenetic or Hematologic Resistance to Imatinib in Patients With Chronic Myeloid Leukemia

BACKGROUND: Although many patients with chronic myeloid leukemia (CML) respond well to imatinib therapy, a significant proportion loses their initial response. Loss of response on imatinib is often because of BCP-ABL mutations. Dasatinib is a 325-fold more potent inhibitor of Bcr-Abl than imatinib and has been associated with high rates of durable responses in patients with CML in chronic phase (CP) after imatinib failure. METHODS: To determine the optimal time for initiating dasatinib after loss of response on imatinib, data from dasatinib trials in CML-CP were analyzed. Patients were grouped according to whether they received early intervention with dasatinib (ie, after cytogenetic recurrence on imatinib), rather than after both cytogenetic and hematologic recurrence. RESULTS: Overall, 72% of patients who received dasatinib after loss of a major cytogenetic response (MCyR) on imatinib achieved a complete cytogenetic response (CCyR) compared with 42% of patients who were treated after loss of both MCyR and complete hematologic response (CHR). Event-free survival (EFS) also was higher after earlier dasatinib treatment (24-month EFS rates: 89% after loss of MCyR on imatinib vs 29% after loss of both MCyR and CHR). Among patients who were treated after loss of CHR on imatinib with no prior MCyR, 26% achieved a CCyR with dasatinib, and the 24-month EFS rate was 64%. In all 3 groups, CCyR rates were similar in patients with or without pre-existing BCP-ABL mutations. CONCLUSIONS: The results of the current study suggested that optimal outcomes are achieved when dasatinib is administered early after imatinib resistance. Cancer 2009;115:2912-21. (C) 2009 American Cancer Society.