EFFICACY AND SAFETY OF DASATINIB VS IMATINIB IN PATIENTS WITH NEWLY DIAGNOSED CHRONIC MYELOID LEUKEMIA IN CHRONIC PHASE (CML-CP): EUROPEAN SUBPOPULATION ANALYSIS OF THE PHASE 3 DASISION TRIAL

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Background. In the phase 3 DASISION trial of dasatinib vs imatinib in patients with newly diagnosed CML-CP, dasatinib demonstrated higher 12-month rates of complete cytogenetic response (CCyR) and major molecular response (MMR), lower rates of transformation, and was well tolerated (Kantarjian NEJM 2010 362 2260). Aims. Assess efficacy and safety of dasatinib vs imatinib in European patients from DASISION. Methods. After informed consent, patients were randomized to dasatinib 100 mg once daily (n=259) or imatinib 400 mg once daily (n=260). 170 patients enrolled were from European countries (France: n=41; Spain: n=30; Czech Republic: n=22; Poland: n=20; Italy: n=14; Germany n=12; Belgium: n=9; Hungary: n=6; The Netherlands: n=6; Austria: n=4; Denmark: n=4; Greece: n=2), with 74 and 96 patients receiving dasatinib and imatinib, respectively. Primary endpoint was confirmed CCyR (cCCyR) by 12 months. Results. In the European subpopulation and total population, 82% vs 75% and 77% vs 66% of dasatinib vs imatinib patients achieved cCCyR by 12 months, respectively. After 24 months, 73% and 72% of European patients and 77% and 75% of total patients receiving dasatinib and imatinib, respectively, remained on therapy. Respective 24-month cumulative rates of MMR in the European subpopulation and total population for dasatinib vs imatinib were 61% vs 48% and 64% vs 46%, respectively. Median time to MMR calculated using competing risk analysis in European patients was shorter for dasatinib (12 months) than imatinib (30 months). Among European patients, no patient receiving dasatinib transformed to accelerated/blast phase (AP/BP) on study or during follow-up after discontinuation, compared with four (4.2%) patients receiving imatinib. In the total population, nine (3.5%) vs 15 (5.8%) patients receiving dasatinib vs imatinib transformed. Drug-related adverse events (AEs) are shown (Table 1). Grade 3/4 non-hematologic AE rates were ≤1%. For dasatinib vs imatinib, in the European population (total population), 43% vs 29% (59% vs 43%) had dose interruption, 22% vs 16% (28% vs 15%) had dose reduction, and 11% vs 6% (7% vs 5%) discontinued due to AEs. Minimum 36- month follow-up will be presented. Conclusions. After 24 months dasatinib showed higher efficacy compared with imatinib, lower transformations to AP/BP, and was generally well tolerated. The efficacy and safety of dasatinib in the European subpopulation was similar to the total population, supporting first-line dasatinib use in European patients with newly diagnosed CML-CP.

Table 1. *myalgia, muscle spasms, and musculoskeletal pain.

Haematologica, 2012; 97(s1):  75