Midostaurin plus Chemotherapy for Acute Myeloid Leukemia with a FLT3 Mutation
Richard Stone,Sumithra J. Mandrekar,Ben L. Sanford,Kristina Laumann,Susan Geyer,Clara D. Bloomfield,Christian Thiede,Thomas W. Prior,Konstanze Döhner,Guido Marcucci,Francesco Lo-Coco,Rebecca B. Klisovic,Andrew H. Wei,Jorge Sierra,Miguel A. Sanz,Joseph Brandwein,Theo de Witte,Dietger Niederwieser,Frederick R. Appelbaum,Bruno C. Medeiros,Martin S. Tallman,Jürgen Krauter,Richard F. Schlenk,Arnold Ganser,Hubert Serve,Gerhard Ehninger,Sergio Amadori,Richard A. Larson,Hartmut Döhner +28 more
TLDR
The addition of the multitargeted kinase inhibitor midostaurin to standard chemotherapy significantly prolonged overall and event‐free survival among patients with AML and a FLT3 mutation.Abstract:
BackgroundPatients with acute myeloid leukemia (AML) and a FLT3 mutation have poor outcomes. We conducted a phase 3 trial to determine whether the addition of midostaurin — an oral multitargeted kinase inhibitor that is active in patients with a FLT3 mutation — to standard chemotherapy would prolong overall survival in this population. MethodsWe screened 3277 patients, 18 to 59 years of age, who had newly diagnosed AML for FLT3 mutations. Patients were randomly assigned to receive standard chemotherapy (induction therapy with daunorubicin and cytarabine and consolidation therapy with high-dose cytarabine) plus either midostaurin or placebo; those who were in remission after consolidation therapy entered a maintenance phase in which they received either midostaurin or placebo. Randomization was stratified according to subtype of FLT3 mutation: point mutation in the tyrosine kinase domain (TKD) or internal tandem duplication (ITD) mutation with either a high ratio (>0.7) or a low ratio (0.05 to 0.7) of muta...read more
Citations
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Functional genomic landscape of acute myeloid leukaemia
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Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet.
Hartmut Döhner,Elihu H. Estey,Sergio Amadori,Frederick R. Appelbaum,Thomas Büchner,Alan Kenneth Burnett,Hervé Dombret,Pierre Fenaux,David Grimwade,Richard A. Larson,Francesco Lo-Coco,Tomoki Naoe,Dietger Niederwieser,Gert J. Ossenkoppele,Miguel A. Sanz,Jorge Sierra,Martin S. Tallman,Bob Löwenberg,Clara D. Bloomfield +18 more
TL;DR: An international expert panel is provided to provide updated evidence- and expert opinion-based recommendations for the diagnosis and management of AML, that contain both minimal requirements for general practice as well as standards for clinical trials.
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TL;DR: Genetic predictors of outcome that improved risk stratification among patients with AML, independently of age, white-cell count, induction dose, and post-remission therapy, are identified and the significance of these predictors in an independent cohort is validated.
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Refinement of cytogenetic classification in acute myeloid leukemia: determination of prognostic significance of rare recurring chromosomal abnormalities among 5876 younger adult patients treated in the United Kingdom Medical Research Council trials
David Grimwade,Robert Kerrin Hills,Anthony V. Moorman,Helen Walker,S Chatters,Anthony H. Goldstone,Keith Wheatley,Christine J. Harrison,Alan Kenneth Burnett +8 more
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