Midostaurin added to chemotherapy and continued single-agent maintenance therapy in acute myeloid leukemia with FLT3-ITD

Schlenk RF, Weber D, Fiedler W, Salih HR, Wulf G, Salwender H, Schroeder T, Kindler T, Luebber M, Wolf D, Westermann J, Kraemer D, Goetze KS, Horst HA, Krauter J, Girschikofsky M, Ringhoffer M, Suedhoff T, Held G, Derigs HG, Schroers R, Greil R, Griesshammer M, Lange E, Burchardt A, Martens U, Hertenstein B, Marretta L, Heuser M, Thol F, Gaidzik V, Herr W, Krzykalla J, Benner A, Doehner K, Ganser A, Paschka P, Doehner H (2019)

Publication Type: Journal article

Publication year: 2019

Journal

Book Volume: 133

Pages Range: 840-851

Journal Issue: 8

DOI: 10.1182/blood-2018-08-869453

Abstract

Patients with acute myeloid leukemia (AML) and a FLT3 internal tandem duplication (ITD) have poor outcomes to current treatment. A phase 2 hypothesis-generating trial was conducted to determine whether the addition of the multitargeted kinase inhibitor midostaurin to intensive chemotherapy followed by allogeneic hematopoietic cell transplantation (alloHCT) and single-agent maintenance therapy of 12 months is feasible and favorably influences event-free survival (EFS) compared with historical controls. Patients 18 to 70 years of age with newly diagnosed AML and centrally confirmed FLT3-ITD were eligible: 284 patients were treated, including 198 younger (18-60 years) and 86 older (61-70 years) patients. Complete remission (CR) rate, including CR with incomplete hematological recovery (CRi) after induction therapy, was 76.4% (younger, 75.8%; older, 77.9%). The majority of patients in CR/CRi proceeded to alloHCT (72.4%). Maintenance therapy was started in 97 patients (34%): 75 after alloHCT and 22 after consolidation with high-dose cytarabine (HiDAC). Median time receiving maintenance therapy was 9 months after alloHCT and 10.5 months after HiDAC; premature termination was mainly a result of nonrelapse causes (gastrointestinal toxicity and infections). EFS and overall survival at 2 years were 39% (95% confidence interval [CI], 33%-47%) and 34% (95% CI, 24%-47%) and 53% (95% CI, 46%-61%) and 46% (95% CI, 35%-59%) in younger and older patients, respectively. EFS was evaluated in comparison with 415 historical controls treated within 5 prospective trials. Propensity score-weighted analysis revealed a significant improvement of EFS by midostaurin (hazard ratio [HR], 0.58; 95% CI, 0.48-0.70; P < .001) overall and in older patients (HR, 0.42; 95% CI, 0.29-0.61). The study was registered at www.clinicaltrials.gov as #NCT01477606.

Involved external institutions

Charité - Universitätsmedizin Berlin Germany (DE) Paracelsus-Elena-Klinik Kassel Germany (DE) Deutsches Krebsforschungszentrum (DKFZ) Germany (DE) Universitätsklinikum Ulm Germany (DE) Eberhard Karls Universität Tübingen Germany (DE) Heinrich-Heine-Universität Düsseldorf Germany (DE) Universitätsklinikum Bonn Germany (DE) Städtisches Klinikum Karlsruhe Germany (DE) Universitätsklinikum Hamburg-Eppendorf (UKE) Germany (DE) Universitätsklinikum Göttingen Germany (DE) Asklepios Klinik Altona Germany (DE) Klinikum Oldenburg Germany (DE) Klinikum rechts der Isar Germany (DE) Universitätsklinikum Schleswig-Holstein (UKSH) Germany (DE) Medizinische Hochschule Hannover (MHH) / Hannover Medical School Germany (DE) Ordensklinikum Linz - Elisabethinen Austria (AT) Klinikum Passau Germany (DE) Universitätsklinikum des Saarlandes (UKS) Germany (DE) Paracelsus Medizinische Privatuniversität Austria (AT) Albert-Ludwigs-Universität Freiburg Germany (DE) Universitätsklinikum Knappschaftskrankenhaus Bochum Germany (DE) Klinikum Frankfurt Höchst Germany (DE) SLK-Kliniken Heilbronn GmbH Germany (DE) Johannes Wesling Klinikum Minden Germany (DE) Evangelisches Krankenhaus Hamm Germany (DE) Universitätsklinikum Gießen und Marburg (UKGM) Germany (DE) Klinikverbund Bremen (Gesundheit Nord) Germany (DE) Vivantes - Netzwerk für Gesundheit GmbH Germany (DE)

How to cite

APA:

Schlenk, R.F., Weber, D., Fiedler, W., Salih, H.R., Wulf, G., Salwender, H.,... Doehner, H. (2019). Midostaurin added to chemotherapy and continued single-agent maintenance therapy in acute myeloid leukemia with FLT3-ITD. Blood, 133(8), 840-851. https://doi.org/10.1182/blood-2018-08-869453

MLA:

Schlenk, Richard F., et al. "Midostaurin added to chemotherapy and continued single-agent maintenance therapy in acute myeloid leukemia with FLT3-ITD." Blood 133.8 (2019): 840-851.

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