Efficacy and Safety of Dasatinib in Patients with Chronic Myeloid Leukemia in Blast Phase Whose Disease Is Resistant or Intolerant to Imatinib: 2-Year Follow-Up Data from the START Program.

Abstract The prognosis for patients with myeloid-blast (MB) or lymphoid-blast (LB) chronic myeloid leukemia (CML) is poor, with an estimated survival from onset of blast crisis of approximately 3 months. Dasatinib (SPRYCEL®) is a novel inhibitor of BCR-ABL and SRC-family kinases, that has proven to be effective (in terms of complete hematologic and cytogenetic response) for patients with MB- or LB-CML whose disease is either resistant or intolerant to imatinib. Patients were enrolled to the corresponding START studies between January and June 2005, and dasatinib 70 mg BID was administered to 109 patients with MB-CML and 48 patients with LB-CML. All patients had previously failed treatment with imatinib - 90% of whom were resistant to imatinib. Here we present an update with a minimum follow-up of 12 mo. Of the 157 patients, 56% were male and median age was 54 years (range 17–81). Median time from CML diagnosis was 44 mo (range 2–216). Prior therapy included imatinib >600 mg/d in 50% of patients, treatment with imatinib for >3 years in 36%, and stem-cell transplantation in 19%. At baseline, 57% had WBC <20,000/mm3, 69% had platelets <100,000/mm3, and 18% had extramedullary disease outside of the spleen. Major hematologic responses (MaHRs) were induced in 34% of patients with MB-CML (imatinib-resistant 35%, -intolerant 20%) and 35% of LB-CML patients (imatinib-resistant 36%, -intolerant 33%). Major cytogenetic responses (MCyRs) were attained in 33% of patients with MB-CML (imatinib-resistant 34%, -intolerant 20%) and 52% of LB-CML patients (imatinib-resistant 50%, -intolerant 67%), while complete cytogenetic responses (CCyRs) were achieved in 26% (imatinib-resistant 26%, -intolerant 20%) and 46% of patients (imatinib-resistant 43%, -intolerant 67%), respectively. Median progression-free survival was 6.7 mo (MB-CML) and 3.0 mo (LB-CML) while median overall survival was 11.8 mo and 5.3 mo, respectively. Dasatinib was generally well tolerated in this poor prognosis population. Fluid retention events were observed more frequently in the MB-CML cohort, with all grade pleural effusion occurring in 36% and 13% of MB and LB patients, respectively (grade 3–4 - 15% and 6%). Other non-hematologic side effects were primarily grade 1–2. Cytopenias were noted for the majority of patients, and were manageable; grade 3–4 febrile neutropenia was recorded in 8% of patients. Dasatinib doses were reduced in 32% of patients and interrupted in 59%, most typically as a result of non-hematologic toxicities. Doses were escalated in 44% of patients. The median duration of therapy was 3.4 mo (0.03–18) for all patients and 14 mo (6–18) for patients still receiving treatment. Long-term data confirm that dasatinib is highly active, producing rapid and clinically meaningful responses in this poor prognosis patient population. Updated analyses corresponding to a minimum follow-up of 2 years on all patients will be presented.

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