Low-Dose Dasatinib 50 mg Daily Versus Standard-Dose Dasatinib 100 mg Daily in Newly Diagnosed Chronic Myeloid Leukemia: A Propensity Score Analysis

Context Low-dose dasatinib was shown to be safe and effective in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP). There are no randomized clinical trials to compare the outcome with the standard-dose dasatinib. Objective The aim of this study is to compare responses and outcome of patients with newly diagnosed CML-CP treated with frontline dasatinib 50 mg/day with those who received standard-dose dasatinib 100 mg/day. Design Propensity score analysis with 1:1 matching was performed with the nearest neighbor-matching method using calipers of width equal to 0.2. Setting MD Anderson Cancer Center. Patients or other participants We analyzed 233 patients with newly diagnosed CML-CP who were treated with low-dose dasatinib 50 mg/day (N=83) or standard-dose dasatinib 100 mg/day (N=150). Interventions Patients on low-dose dasatinib who had suboptimal response by European LeukemiaNet criteria had an option to increase the dose to 100 mg/day. Main outcome measures Responses criteria were previously defined. Failure-free survival (FFS) was calculated from the start date of therapy to the dates of treatment discontinuation for any reason except of treatment-free remission; event-free survival (EFS), to the date of any of the events while on study as defined in the IRIS study; transformation-free survival (TFS), to the date of transformation to advanced stage or death during study; overall survival (OS), to the date of death from any cause at any time or date of last follow-up. Results The overall median follow-up was 84 months: 24 months and 120 months for low-dose and standard-dose, respectively. Propensity score matching identified 77 patients in each cohort without significant baseline difference. The 12-month MMR rates were 82% and 76% for low-dose and standard-dose groups, respectively. The cumulative incidence of MR4, MR4.5, CMR rates within 1 year were higher in the low-dose dasatinib group compared with the standard-dose group (63% and 43%, 53% and 37%, and 24% and 11% for each). The 2-year FFS rates were 96% and 84%, respectively (P=0.011). The TFS, EFS, and OS rates were similar. Conclusions The low-dose dasatinib is at least as good as standard-dose dasatinib with better safety profile, resulting in better outcome.