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DASISION (Dasatinib vs. Imatinib Study in Treatment-Naive Chronic Myeloid Leukemia Patients) was an open-label, multicenter, international randomized trial conducted in adult patients with newly diagnosed CP CML. A total of 519 patients were randomly assigned to receive dasatinib 100 mg once daily or imatinib 400 mg once daily. Patients with a history of heart disease were included in the trial, except those who had experienced a myocardial infarction within 6 months, congestive heart failure within 3 months, significant arrhythmia, or QTc prolongation.
The primary endpoint was the rate of confirmed complete cytogenetic response (CCyR) within 12 months. A confirmed CCyR was defined as a CCyR observed on two consecutive occasions at least 28 days apart.
The median age was 46 years in the dasatinib group and 49 years in the imatinib group; 10% and 11% of patients, respectively, were aged ≥65 years. There were slightly more male patients than female patients in both groups (59% vs. 41%). Among all patients, 53% were White and 39% were Asian. At baseline, the distribution of Hasford risk scores was similar between the dasatinib and imatinib treatment groups (low risk: 33% vs. 34%; intermediate risk: 48% vs. 47%; high risk: 19% vs. 19%).
At a minimum follow-up of 12 months, 85% of patients randomized to dasatinib and 81% of those randomized to imatinib remained in the study. At a minimum follow-up of 24 months, 77% of dasatinib-randomized patients and 75% of imatinib-randomized patients stayed in the study; at a minimum follow-up of 60 months, 61% and 62% of patients, respectively, were still receiving treatment at study closure.
Confirmed CCyR rate within 12 months: 76.8% (95% CI: 71.2–81.8) in the dasatinib group (n=259) vs. 66.2% (95% CI: 60.1–71.9) in the imatinib group (n=260); P=0.007.
Major molecular response (MMR) rate at 12 months: 52.1% (95% CI: 45.9–58.3) in the dasatinib group vs. 33.8% (95% CI: 28.1–39.9) in the imatinib group; P<0.0001.
MMR rate at 60 months: 76.4% (95% CI: 70.8–81.5) in the dasatinib group vs. 64.2% (95% CI: 58.1–70.1) in the imatinib group.
Confirmed CCyR rates at 24, 36, and 60 months: 80% vs. 74%, 83% vs. 77%, and 83% vs. 79% in the dasatinib group vs. the imatinib group, respectively.
MMR rates at 24 and 36 months: 65% vs. 50% and 69% vs. 56% in the dasatinib group vs. the imatinib group, respectively.
The median time to confirmed CCyR was 3.1 months in 215 dasatinib responders and 5.8 months in 204 imatinib responders.
The median time to MMR was 9.3 months in 198 dasatinib responders and 15.0 months in 167 imatinib responders.
At 60 months, 8 patients (3%) in the dasatinib group progressed to accelerated phase (AP) or blast phase (BP), compared with 15 patients (6%) in the imatinib group.
The estimated 60-month survival rates were 90.9% (CI: 86.6%–93.8%) in the dasatinib group and 89.6% (CI: 85.2%–92.8%) in the imatinib group. Based on data 5 years after the last patient was enrolled in the trial:
83% of patients in the dasatinib group and 77% in the imatinib group were known to be alive.
10% of patients in both groups were known to have died.
7% of patients in the dasatinib group and 13% in the imatinib group had unknown survival status.
At 60 months of follow-up in the dasatinib group, the MMR rates at any time by Hasford risk group were: 90% (low risk), 71% (intermediate risk), and 67% (high risk). In the imatinib group, the MMR rates at any time by Hasford risk group were: 69% (low risk), 65% (intermediate risk), and 54% (high risk).
BCR-ABL sequencing was performed on blood samples from patients who discontinued dasatinib or imatinib treatment in the newly diagnosed trial. Mutations detected in dasatinib-treated patients included T315I, F317I/L, and V299L. Based on in vitro data, dasatinib does not appear to have activity against the T315I mutation.
FDA，2024.07
