Midostaurin plus intensive chemotherapy for younger and older patients with AML and FLT3 internal tandem duplications

Hartmut Döhner, Daniela Weber, Julia Krzykalla, Walter Fiedler, Gerald Wulf, Helmut Salih, Michael Lübbert, Michael W.M. Kühn, Thomas Schroeder, Hans Salwender, Katharina Götze, Jörg Westermann, Lars Fransecky, Karin Mayer, Bernd Hertenstein, Mark Ringhoffer, Hans Joachim Tischler, Sigrid Machherndl-Spandl, Anika Schrade, Peter PaschkaVerena I. Gaidzik, Frauke Theis, Felicitas Thol, Michael Heuser, Richard F. Schlenk, Lars Bullinger, Maral Saadati, Axel Benner, Richard Larson, Richard Stone, Konstanze Döhner, Arnold Ganser

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


We conducted a single-arm, phase 2 trial (German-Austrian Acute Myeloid Leukemia Study Group [AMLSG] 16-10) to evaluate midostaurin with intensive chemotherapy followed by allogeneic hematopoietic-cell transplantation (HCT) and a 1-year midosta urin maintenance therapy in adult patients with acute myeloid leukemia (AML) and fms-related tyrosine kinase 3 (FLT3) internal tandem duplication (ITD). Patients 18 to 70 years of age with newly diagnosed FLT3-ITD-positive AML were eligible. Primary and key secondary endpoints were event-free survival (EFS) and overall survival (OS). Results were compared with 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 with patients (18-59 years) treated on the placebo arm of the Cancer and Leukemia Group B (CALGB) 10603/RATIFY trial. The trial accrued 440 patients (18-60 years, n = 312; 61-70 years, n = 128). In multivariate analysis, EFS was significantly in favor of patients treated within the AMLSG 16-10 trial compared with the AMLSG control (hazard ratio [HR], 0.55; P <.001); both in younger (HR, 0.59; P < .001) and older patients (HR, 0.42; P < .001). Multivariate analysis also showed a significant beneficial effect on OS compared with the AMLSG control (HR, 0.57; P < .001) as well as to the CALGB 10603/RATIFY trial (HR, 0.71; P = .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 with 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.

Original languageEnglish
Pages (from-to)5345-5355
Number of pages11
JournalBlood Advances
Issue number18
StatePublished - 27 Sep 2022


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