Follow-Up Results Support Potential Use of Dasatinib As Initial Therapy for Patients Newly Diagnosed With Chronic-Phase Chronic Myeloid Leukemia

ORLANDO, Fla.—Dasatinib continues to demonstrate superior efficacy compared with imatinib as initial treatment for patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP), results of an 18-month follow-up of the phase 3 DASISION comparative trial have shown.

Dasatinib also continues to be generally well tolerated. These results support potential use of dasatinib as initial treatment for this patient population, said Neil Shah, MD, PhD, of the University of California San Francisco School of Medicine, San Francisco, Calif.

Dasatinib, an established second-line treatment for patients with CML-CP who are resistant, intolerant, or have a suboptimal response to imatinib is 325-fold more potent than imatinib in vitro against unmutated BCR-ABL. After a minimum of 12 months of follow-up, patients in the DASISION study who were treated with dasatinib 100 mg once daily had significantly higher and faster rates of complete cytogenetic response (CCyR) and major molecular response (MMR) compared with imatinib 400 mg once daily, Dr. Shah told those attending the 52nd American Society of Hematology Annual Meeting and Exposition.

The DASISION study randomized 519 patients with newly diagnosed CML-CP (median disease duration of 1 month) stratified by Hasford risk to either dasatinib 100 mg once daily (n=259) or imatinib 400 mg once daily (n=260). For the current analysis, median treatment duration was 18 months for each drug; 81% of patients in the dasatinib arm and 80% in the imatinib arm remained on study drug. Median dose intensity was 99 mg/day for dasatinib and 400 mg/day for imatinib.

Efficacy and safety results in this analysis were consistent with those reported previously after 12 months of follow-up, Dr. Shah said. By 18 months, rate of confirmed CCyR (cCCyR, CCyR on consecutive analyses at least 1 month apart) continued to be higher for dasatinib than for imatinib (78% vs 70%); P=0.0366). Based on time-in-cCCyR (a measure of durability) analysis involving all randomized patients, those treated with dasatinib were 28% less likely to experience a progression event (as defined by European LeukemiaNet. 2006) after achieving a cCCyR or never achieving a cCCyR compared with those on imatinib.

The rate of MMR at any time point was superior for dasatinib compared with imatinib (57% vs 41%, P=0.0002). Based on time-to-response analysis, patients on dasatinib were 1.84-fold more likely to achieve a MMR than those on imatinib (HR=1.84, P<0.0001). Rates of cCCYR in low-risk patients treated with dasatinib were 92%; for intermediate risk, 71%; and high risk, 73%. Corresponding rates in the imatinib arm were 72%, 71%, and 64%. Rates of MMR in dasatinib-treated patients low, intermediate, and high risk were 63%, 56% and 51%, respectively. Corresponding rates in the imatinib arm were 48%, 40%, and 30%. A BCR-ABL transcript level of ≤0.0032% was achieved in 13% of patients treated with dasatinib and 7% with imatinib.

At 18 months, rates of progression-free survival were 94.9% for dasatinib and 93.7% for imatinib. Overall survival rates were 96.0% for dasatinib and 97.9% for imatinib. Six patients (2.3%) in the dasatinib arm and 11 (4.3%) in the imatinib arm discontinued due to treatment failure as defined by 2006 European LeukemiaNet criteria. Six patients (2.3%) on dasatinib and 9 (3.5%) on imatinib had a transformation to accelerated or blast phase.

Discontinuation of treatment due to drug-related adverse events (AEs) was infrequent for both dasatinib (6%) and imatinib (4%). Nonhematologic AEs (all grades) in ≥10% of pts (dasatinib vs imatinib) were fluid retention (23% vs 43%), diarrhea (18% vs 19%), nausea (9% vs 21%), vomiting (5% vs 10%), muscle inflammation (4% vs 19%), myalgia (6% vs 12%), musculoskeletal pain (12% vs 16%), fatigue (8% vs 11%), and rash (11% vs 17%). Although superficial edema occurred less frequently with dasatinib than imatinib (10% vs 36%), pleural effusion was observed only with dasatinib (12% vs 0%: grade 1, 2%; grade 2, 9%; grade 3, <1%), and efficacy was not affected. Nonhematologic grade 3/4 AEs were infrequent in either arm (≤1%).

Grade 3/4 cytopenias (dasatinib vs imatinib) were anemia (11% vs 7%), neutropenia (22% vs 20%), and thrombocytopenia (19% vs 10%); grade 3/4 bleeding occurred in 2 patients (0.8%) on dasatinib and 3 (1.2%) on imatinib. Six patients on the dasatinib arm (2.3%) and 3 on the imatinib arm (1.2%) discontinued due to cytopenia. There were 11 deaths in the dasatinib arm and 6 deaths in the imatinib arm.