Journal Article

DKFZ-2022-00865

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Midostaurin plus intensive chemotherapy for younger and older Patients with AML and FLT3 internal tandem duplications.

Döhner, H. ; Weber, D. ; Krzykalla, J.DKFZ* ; Fiedler, W. ; Wulf, G. G. ; Salih, H. R. ; Lübbert, M. ; Kühn, M. ; Schroeder, T. ; Salwender, H. ; Götze, K. S. ; Westermann, J. ; Fransecky, L. ; Mayer, K. ; Hertenstein, B. ; Ringhoffer, M. ; Tischler, H.-J. ; Machherndl-Spandl, S. ; Schrade, A. ; Paschka, P. ; Gaidzik, V. I. ; Theis, F. ; Thol, F. R. ; Heuser, M. ; Schlenk, R. F.DKFZ* ; Bullinger, L. ; Saadati, M. ; Benner, A.DKFZ* ; Larson, R. A. ; Stone, R. M. ; Döhner, K. ; Ganser, A.

2022
American Society of Hematology Washington, DC

This record in other databases:  

Please use a persistent id in citations: doi:10.1182/bloodadvances.2022007223

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.

Note: 2022 Sep 27;6(18):5345-5355

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Contributing Institute(s):

1. C060 Biostatistik (C060)
2. Klinische Studienzentrale (W010)

Research Program(s):

1. 313 - Krebsrisikofaktoren und Prävention (POF4-313) (POF4-313)

Appears in the scientific report 2022

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Essential Science Indicators ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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