TY  - JOUR
AU  - Döhner, Hartmut
AU  - Weber, Daniela
AU  - Krzykalla, Julia
AU  - Fiedler, Walter
AU  - Wulf, Gerald Georg
AU  - Salih, Helmut R
AU  - Lübbert, Michael
AU  - Kühn, Michael
AU  - Schroeder, Thomas
AU  - Salwender, Hans
AU  - Götze, Katharina S
AU  - Westermann, Jörg
AU  - Fransecky, Lars
AU  - Mayer, Karin
AU  - Hertenstein, Bernd
AU  - Ringhoffer, Mark
AU  - Tischler, Hans-Joachim
AU  - Machherndl-Spandl, Sigrid
AU  - Schrade, Anika
AU  - Paschka, Peter
AU  - Gaidzik, Verena I
AU  - Theis, Frauke
AU  - Thol, Felicitas R
AU  - Heuser, Michael
AU  - Schlenk, Richard F
AU  - Bullinger, Lars
AU  - Saadati, Maral
AU  - Benner, Axel
AU  - Larson, Richard A
AU  - Stone, Richard M
AU  - Döhner, Konstanze
AU  - Ganser, Arnold
TI  - Midostaurin plus intensive chemotherapy for younger and older Patients with AML and FLT3 internal tandem duplications.
JO  - Blood advances
VL  - 6
IS  - 18
SN  - 2473-9529
CY  - Washington, DC
PB  - American Society of Hematology
M1  - DKFZ-2022-00865
SP  - 5345-5355
PY  - 2022
N1  - 2022 Sep 27;6(18):5345-5355
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:35486475
DO  - DOI:10.1182/bloodadvances.2022007223
UR  - https://inrepo02.dkfz.de/record/179738
ER  -