Adding dasatinib to intensive treatment in core-binding factor acute myeloid leukemia-results of the AMLSG 11-08 trial

作者：Paschka Peter; Schlenk Richard F; Weber Daniela; Benner Axel; Bullinger Lars; Heuser Michael; Gaidzik Verena I; Thol Felicitas; Agrawal Mridul; Teleanu Veronica; Luebbert Michael; Fiedler Walter; Radsak Markus; Krauter Juergen; Horst Heinz A; Greil Richard; Mayer Karin; Kuendgen Andrea; Martens Uwe; Heil Gerhard; Salih Helmut R; Hertenstein Bernd; Schwaenen Carsten; Wulf Gerald; Lange Elisabeth; Pfreundschuh Michael; Ringhoffer Mark; Girschikofsky Michael

来源：Leukemia, 2018, 32(7): 1621-1630.

DOI：10.1038/s41375-018-0129-6

In this phase Ib/IIa study (ClinicalTrials.gov Identifier: NCT00850382) of the German-Austrian AML Study Group (AMLSG) the multikinase inhibitor dasatinib was added to intensive induction and consolidation chemotherapy and administered as single agent for 1-year maintenance in first-line treatment of adult patients with core-binding factor (CBF) acute myeloid leukemia (AML). The primary combined end point in this study was safety and feasibility, and included the rates of early (ED) and hypoplastic (HD) deaths, pleural/pericardial effusion 3 degrees/4 degrees and liver toxicity 3 degrees/4 degrees, and the rate of refractory disease. Secondary end points were cumulative incidence of relapse (CIR) and death in complete remission (CID), and overall survival (OS). Eighty-nine pts [median age 49.5 years, range: 19-73 years; t(8; 21), n = 37; inv (16), n = 52] were included. No unexpected excess in toxicity was observed. The rates of ED/HD and CR/CRi were 4.5% (4/89) and 94% (84/89), respectively. The 4-year estimated CIR, CID, and OS were 33.1% [95%-CI (confidence interval), 22.7-43.4%], 6.0% (95% CI, 0.9-11.2%), and 74.7% (95% CI, 66.1-84.5%), respectively. On the basis of the acceptable toxicity profile and favorable outcome in the AMLSG 11-08 trial, a confirmatory randomized phase III trial with dasatinib in adults with CBF-AML is ongoing (ClinicalTrials.gov Identifier: NCT02013648).

• 出版日期2018-7