Dasatinib or imatinib in newly diagnosed chronic-phase chronic myeloid leukemia: 2-year follow-up from a randomized phase 3 trial (DASISION)

Abstract

Dasatinib is a highly potent BCR-ABL inhibitor with established efficacy and safety in imatinib-resistant/-intolerant patients with chronic myeloid leukemia (CML). In the phase 3 DASISION trial, patients with newly diagnosed chronicphase (CP) CML were randomized to receive dasatinib 100 mg (n ‫؍‬ 259) or imatinib 400 mg (n ‫؍‬ 260) once daily. Primary data showed superior efficacy for dasatinib compared with imatinib after 12 months, including significantly higher rates of complete cytogenetic response (CCyR), confirmed CCyR (primary end point), and major molecular response (MMR). Here, 24-month data are presented. Cumulative response rates by 24 months in dasatinib and imatinib arms were: CCyR in 86% versus 82%, MMR in 64% versus 46%, and BCR-ABL reduction to < 0.0032% (4.5-log reduction) in 17% versus 8%. Transformation to accelerated-/ blast-phase CML on study occurred in 2.3% with dasatinib versus 5.0% with imatinib. BCR-ABL mutations, assessed after discontinuation, were detected in 10 patients in each arm. In safety analyses, fluid retention, superficial edema, myalgia, vomiting, and rash were less frequent with dasatinib compared with imatinib, whereas pleural effusion and grade 3/4 thrombocytopenia were more frequent with dasatinib. Overall, dasatinib continues to show faster and deeper responses compared with imatinib, supporting first-line use of dasatinib in patients with newly diagnosed CML-CP. This study was registered at

Standardized definitions of molecular response in chronic myeloid leukemia

“…10 By 24 months, CMR 4.5 was achieved in 17% and 8% of patients treated with dasatinib or imatinib (P ¼ 0.002 vs imatinib). 15 Similar response to dasatinib has also been demonstrated in the phase 2 MDACC trial, with 6% of patients achieving CMR 4.5 by 18 months, 7 and in the Southwestern Oncology Group trial, with 27% of patients achieving CMR 4 at 12 months in evaluable patients (P ¼ 0.31 vs imatinib). 8 Taken together, these results demonstrate that the difference in the rates of response between second-generation TKIs and imatinib becomes more pronounced as the depth of MR increases.…”

Discontinuation of tyrosine kinase inhibitors in chronic myeloid leukemia: when is this a safe option to consider?

“…17,26 Table 3, where the percentages of patients who achieved specific molecular responses on IM, nilotinib, and dasatinib on either the ENESTnd or DASISION trial are listed, highlights the increasing relevance of the question of whether TKI therapy can be stopped. [2][3][4][5][43][44][45][46] With 48 months of follow-up, ϳ 40% of patients on second-generation TKIs achieve MR4.5. 44 As may be expected, achievement of MR4.5 occurs later with IM therapy, but 23% of patients treated with IM on ENESTnd achieved these deep molecular responses at 4 years and the numbers of patients achieving these responses will likely continue to increase over time.…”

“…1 Durable cytogenetic and molecular responses are observed with IM therapy, and dasatinib and nilotinib have demonstrated earlier and deeper responses compared with IM when used in the frontline setting. [2][3][4][5] One of the most frequently asked questions for patients with durable complete molecular responses (CMRs) is whether they can safely discontinue treatment without relapse of their disease. Before reviewing this issue, it should be noted that various definitions of CMR have been used in clinical trials.…”

Initial treatment for patients with chronic myeloid leukemia

“…7 When dasatinib was tested, first-line treatment compared with imatinib, the responses were faster and superior, and the molecular response was also deeper. 19,20 The follow-up of the patients treated first line with dasatinib is still short, less than 3 years. The major side effects of dasatinib are leucopenia, thrombocytopenia, pleural effusion and pulmonary complications.…”