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@ARTICLE{Dhner:179738,
author = {H. Döhner and D. Weber and J. Krzykalla$^*$ and W. Fiedler
and G. G. Wulf and H. R. Salih and M. Lübbert and M. Kühn
and T. Schroeder and H. Salwender and K. S. Götze and J.
Westermann and L. Fransecky and K. Mayer and B. Hertenstein
and M. Ringhoffer and H.-J. Tischler and S.
Machherndl-Spandl and A. Schrade and P. Paschka and V. I.
Gaidzik and F. Theis and F. R. Thol and M. Heuser and R. F.
Schlenk$^*$ and L. Bullinger and M. Saadati and A.
Benner$^*$ and R. A. Larson and R. M. Stone and K. Döhner
and A. Ganser},
title = {{M}idostaurin plus intensive chemotherapy for younger and
older {P}atients with {AML} and {FLT}3 internal tandem
duplications.},
journal = {Blood advances},
volume = {6},
number = {18},
issn = {2473-9529},
address = {Washington, DC},
publisher = {American Society of Hematology},
reportid = {DKFZ-2022-00865},
pages = {5345-5355},
year = {2022},
note = {2022 Sep 27;6(18):5345-5355},
abstract = {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.},
cin = {C060 / W010},
ddc = {610},
cid = {I:(DE-He78)C060-20160331 / I:(DE-He78)W010-20160331},
pnm = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
pid = {G:(DE-HGF)POF4-313},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:35486475},
doi = {10.1182/bloodadvances.2022007223},
url = {https://inrepo02.dkfz.de/record/179738},
}