Early response with dasatinib or imatinib in chronic myeloid leukemia: 3-year follow-up from a randomized phase 3 trial (DASISION)

Abstract

This analysis explores the impact of early cytogenetic and molecular responses on the outcomes of patients with chronic myeloid leukemia in chronic phase (CML-CP) in the phase 3 DASatinib versus Imatinib Study In treatment-Naive CML patients trial with a minimum follow-up of 3 years. Patients with newly diagnosed CML-CP were randomized to receive 100 mg dasatinib (n = 259) or 400 mg imatinib (n = 260) once daily. The retrospective landmark analysis included patients evaluable at the relevant time point (3, 6, or 12 months). Median time to complete cytogenetic response was 3 vs 6 months with dasatinib vs imatinib. At 3 and 6 months, the proportion of patients with BCR-ABL transcript levels ≤10% was higher in the dasatinib arm. Deeper responses at 3, 6, and 12 months were observed in a higher proportion of patients on dasatinib therapy and were associated with better 3-year progression-free survival and overall survival in both arms. First-line dasatinib resulted in faster and deeper responses compared with imatinib. The achievement of an early molecular response was predictive of improved progression-free survival and overall survival, supporting new milestones for optimal response in patients with early CML-CP treated with tyrosine kinase inhibitors. This study was registered at www.clinicaltrials.gov as NCT00481247.

Figures

Figure 1

CONSORT diagram for the DASISION trial after a minimum follow-up of 36 months. *Reasons for discontinuation are provided in Table 1. Adapted from Kantarjian et al and reproduced with permission from the American Society of Hematology.

Figure 2

PFS and OS based on response at 3 months. (A) PFS according to BCR-ABL transcript levels at 3 months. Among patients receiving dasatinib, 48%, 37%, and 16% achieved BCR-ABL transcript levels ≤1%, >1% to 10%, and >10% at 3 months, respectively. Among patients receiving imatinib, the percentages were 13%, 51%, and 36%, respectively. Four patients (2 in each treatment arm) progressed before the 3-month molecular landmark and were not included in this analysis. (B) OS according to BCR-ABL transcript levels at 3 months. (C) PFS according to cytogenetic response at 3 months. Among patients receiving dasatinib, 67%, 15%, and 19% achieved CCyR, PCyR, and less than PCyR at 3 months, respectively. Among patients receiving imatinib, the percentages were 36%, 31%, and 33%, respectively. In all panels, patients with response data at 3 months and outcome data after 3 months were included in the analysis.

Figure 3

PFS according to BCR-ABL transcript levels at 6 months. Among patients receiving dasatinib, 69%, 19%, and 11% achieved BCR-ABL transcript levels ≤1%, >1% to 10%, and >10% at 6 months, respectively. Among patients receiving imatinib, the percentages were 49%, 34%, and 17%, respectively. Patients with response data at 6 months and outcome data after 6 months were included in the analysis.

Figure 4

PFS according to response at 12 months. Patients with response data at 12 months and outcome data after 12 months were included in the analysis.