Midostaurin plus intensive chemotherapy for younger and older patients with AML and <i>FLT3</i> internal tandem duplications
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- Hartmut Döhner
- 1Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany;
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- Daniela Weber
- 1Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany;
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- Julia Krzykalla
- 2Division of Biostatistics, German Cancer Research Center, Heidelberg, Germany;
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- Walter Fiedler
- 3Hubertus Wald University Cancer Center, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany;
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- Gerald Wulf
- 4Department of Hematology and Oncology, Georg-August-University Göttingen, Göttingen, Germany;
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- Helmut Salih
- 5Department of Hematology and Oncology, Eberhard-Karls University, Tübingen, Germany;
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- Michael Lübbert
- 6Department of Medicine I, Medical Center – University of Freiburg, Freiburg, Germany;
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- Michael W. M. Kühn
- 7Department of Hematology, Medical Oncology & Pneumology, University Medical Center, Johannes Gutenberg-University Mainz, Mainz, Germany;
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- Thomas Schroeder
- 8Department of Hematology, Oncology, and Clinical Immunology, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany;
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- Hans Salwender
- 9Department of Oncology and Hematology, Asklepios Tumorzentrum Hamburg, AK Altona and AK St. Georg, Hamburg, Germany;
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- Katharina Götze
- 10Department of Medicine III, Hematology and Medical Oncology, Technical University of Munich, Munich, Germany;
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- Jörg Westermann
- 11Department of Hematology, Oncology and Tumorimmunology, Charité University Medicine Berlin, Campus Virchow Klinikum, Berlin, Germany;
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- Lars Fransecky
- 12Department of Internal Medicine II, University Hospital Schleswig Holstein, Campus Kiel, Kiel, Germany;
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- Karin Mayer
- 13Department of Hematology, Oncology, University Hospital Bonn, Bonn, Germany;
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- Bernd Hertenstein
- 14Department of Hematology and Oncology, Klinikum Bremen-Mitte, Bremen, Germany;
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- Mark Ringhoffer
- 15Department of Internal Medicine III, Städtisches Klinikum Karlsruhe, Karlsruhe, Germany;
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- Hans-Joachim Tischler
- 16Department of Hematology and Oncology, University Hospital of Minden, Minden, Germany;
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- Sigrid Machherndl-Spandl
- 17Department of Hematology and Oncology, Hospital Elisabethinen Linz, Linz, Austria;
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- Anika Schrade
- 1Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany;
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- Peter Paschka
- 1Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany;
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- Verena I. Gaidzik
- 1Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany;
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- Frauke Theis
- 1Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany;
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- Felicitas Thol
- 18Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany;
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- Michael Heuser
- 18Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany;
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- Richard F. Schlenk
- 19National Center of Tumor Diseases, German Cancer Research Center, Heidelberg, Germany;
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- Lars Bullinger
- 11Department of Hematology, Oncology and Tumorimmunology, Charité University Medicine Berlin, Campus Virchow Klinikum, Berlin, Germany;
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- Maral Saadati
- 21Freelance Statistician, Saadati Solutions, Ladenburg, Germany;
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- Axel Benner
- 2Division of Biostatistics, German Cancer Research Center, Heidelberg, Germany;
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- Richard Larson
- 22Department of Medicine and Comprehensive Cancer Center, University of Chicago, Chicago, IL; and
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- Richard Stone
- 23Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
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- Konstanze Döhner
- 1Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany;
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- Arnold Ganser
- 18Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany;
Abstract
<jats:title>Abstract</jats:title> <jats:p>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. This trial is registered at clinicaltrialsregistry.eu as Eudra-CT number 2011-003168-63 and at clinicaltrials.gov as NCT01477606.</jats:p>
Journal
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- Blood Advances
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Blood Advances 6 (18), 5345-5355, 2022-09-21
American Society of Hematology
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Details 詳細情報について
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- CRID
- 1360861711783831168
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- ISSN
- 24739537
- 24739529
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- Data Source
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- Crossref