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Clinical Trial
. 2014 Jan 23;123(4):494-500.
doi: 10.1182/blood-2013-06-511592. Epub 2013 Dec 5.

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

Elias Jabbour  1 , Hagop M Kantarjian, Giuseppe Saglio, Juan Luis Steegmann, Neil P Shah, Concepción Boqué, Charles Chuah, Carolina Pavlovsky, Jirí Mayer, Jorge Cortes, Michele Baccarani, Dong-Wook Kim, M Brigid Bradley-Garelik, Hesham Mohamed, Mark Wildgust, Andreas Hochhaus
Affiliations
Clinical Trial

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

Elias Jabbour et al. Blood. .

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.

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Figures

Figure 1
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
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
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
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.
See this image and copyright information in PMC

References

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    1. Hochhaus A, Shah NP, Cortes J, et al. Dasatinib versus imatinib (IM) in newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP): DASISION 3-year follow-up. [abstract]. J Clin Oncol. 2012;30(15 suppl) [Abstract 6504]
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