Midostaurin plus intensive chemotherapy for younger and older patients with AML and FLT3 internal tandem duplications
Year: 2022
Type: article
Study design: Clinical Trial
Abstract: 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.
Source: Blood Advances
Authors: 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 Paschka, Verena 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
Institutions: University Hospital Ulm, German Cancer Research Center, University Medical Center Hamburg-Eppendorf, University Cancer Center Hamburg, University of Göttingen, University of Tübingen, University of Freiburg, University Medical Center Freiburg, Johannes Gutenberg University Mainz, University Medical Center of the Johannes Gutenberg University Mainz, Heinrich Heine University Düsseldorf, Asklepios Klinik Altona, Asklepios, Technical University of Munich, Charité – Universitätsmedizin Berlin, University Hospital Schleswig-Holstein, University Hospital Bonn, Klinikum Bremen-Mitte, Städtisches Klinikum Karlsruhe, Johannes Wesling Klinikum Minden, Krankenhaus der Elisabethinen, Medizinische Hochschule Hannover, University Hospital Heidelberg, National Center for Tumor Diseases, University of Chicago, University of Chicago Medicine Comprehensive Cancer Center, Dana-Farber Cancer Institute
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,000
OpenAlex ID: W4225136182