Use of dasatinib in patients (pts) with previously untreated chronic myelogenous leukemia (CML) in chronic phase (CML-CP)

Abstract

7005 Background: Dasatinib (formerly BMS-354825) is a multi-targeted kinase inhibitor of BCR-ABL and SRC. Based on its high level of activity in pts with imatinib (im) resistant/intolerant CML-CP, the present phase II trial was designed to study previously untreated CML-CP pts treated with dasatinib. The primary objective was to estimate the proportion of pts attaining major molecular response (BCR-ABL/ABL ratio =0.05% by qPCR) at 12 months (mo). Methods: All pts received dasatinib orally 100 mg/day, and were randomized to either a 50 mg-twice-daily or a 100 mg-once-daily schedule. Dose escalation to 140 mg/day and 180 mg/day for poor response or dose reduction to 80 mg/day and 40 mg/day for toxicity, maintaining the same schedule, was allowed. Results: Of the 31 pts enrolled between 11/05 and 12/06; 52% were female; median age was 41 years (range 18–76). At 3 mo, complete hematologic response (CHR) and major cytogenetic response both occurred in 21 (81%) of 26 evaluable pts and complete cytogenetic response (CCyR) in 19 (73%) pts. After 6 mo of therapy, 20/21 (95%) evaluable pts had achieved CCyR. This compares favorably with a CCyR at 6 mo of 54% with im 400 mg/day and 85% with im 800 mg/day, in historical data of similar patients treated in studies at MD Anderson. At 9 mo, 4/15 (27%) evaluable pts had achieved a major molecular response. The most common non-hematologic adverse events (AE) included dyspnea (8 pts), fatigue (7 pts), muscle pain (6 pts), and headache (5 pts) and were predominantly grade (gr) 1–2. Pleural effusion occurred in only 3 pts (gr 1–2 in all). Grade 3–4 hematologic toxicity (transient) included anemia in 4 pts, neutropenia in 7 pts, and thrombocytopenia in 4 pts. With a median duration of therapy of 10 mo, 13 pts required transient treatment interruption, 9 due to non-hematologic toxicities, 3 due to hematologic toxicities, and 1 due to both. The actual median daily dose for all pts was 100mg. No difference in AEs has been observed between dose schedules. Conclusions: Rapid, complete cytogenetic responses to dasatinib 100 mg/day have been observed in a high percentage of patients with previously untreated CML- CP. Accrual to this trial continues. No significant financial relationships to disclose.