%0 Journal Article
%A Döhner, Hartmut
%A Weber, Daniela
%A Krzykalla, Julia
%A Fiedler, Walter
%A Wulf, Gerald Georg
%A Salih, Helmut R
%A Lübbert, Michael
%A Kühn, Michael
%A Schroeder, Thomas
%A Salwender, Hans
%A Götze, Katharina S
%A Westermann, Jörg
%A Fransecky, Lars
%A Mayer, Karin
%A Hertenstein, Bernd
%A Ringhoffer, Mark
%A Tischler, Hans-Joachim
%A Machherndl-Spandl, Sigrid
%A Schrade, Anika
%A Paschka, Peter
%A Gaidzik, Verena I
%A Theis, Frauke
%A Thol, Felicitas R
%A Heuser, Michael
%A Schlenk, Richard F
%A Bullinger, Lars
%A Saadati, Maral
%A Benner, Axel
%A Larson, Richard A
%A Stone, Richard M
%A Döhner, Konstanze
%A Ganser, Arnold
%T Midostaurin plus intensive chemotherapy for younger and older Patients with AML and FLT3 internal tandem duplications.
%J Blood advances
%V 6
%N 18
%@ 2473-9529
%C Washington, DC
%I American Society of Hematology
%M DKFZ-2022-00865
%P 5345-5355
%D 2022
%Z 2022 Sep 27;6(18):5345-5355
%X We conducted a single-arm phase-II trial (AMLSG 16-10) to evaluate midostaurin with intensive chemotherapy followed by allogeneic hematopoietic-cell transplantation (HCT) and a one-year midostaurin maintenance therapy in adult patients with acute myeloid leukemia (AML) and FLT3 internal tandem duplication (ITD). Patients 18-70 years of age with newly diagnosed FLT3-ITD-positive AML were eligible. Primary and key secondary endpoints were event-free (EFS) and overall survival (OS). Results were compared to a historical cohort of 415 patients treated on 5 prior AMLSG trials; statistical analysis was performed using a double-robust adjustment with propensity score weighting and covariate adjustment. Results were also compared to patients (18-59yrs) treated on the placebo arm of the CALGB 10603/RATIFY trial. The trial accrued 440 patients (18-60yrs, n=312; 61-70yrs, n=128). In multivariate analysis, EFS was significantly in favor of patients treated within the AMLSG 16-10 trial compared to the AMLSG control (HR 0.55; P<0.001); both in younger (HR 0.59; P<0.001) and older patients (HR 0.42; P<0.001). Multivariate analysis also showed a significant beneficial effect on OS compared to the AMLSG control (HR 0.57; P<0.001) as well as to the CALGB 10603/RATIFY trial (HR 0.71; p=0.005). The treatment effect of midostaurin remained significant in sensitivity analysis including allogeneic HCT as a time-dependent covariate. Addition of midostaurin to chemotherapy was safe in younger and older patients. In comparison to historical controls, the addition of midostaurin to intensive therapy led to a significant improvement in outcome in younger and older patients with AML and FLT3-ITD.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:35486475
%R 10.1182/bloodadvances.2022007223
%U https://inrepo02.dkfz.de/record/179738