Midostaurin in patients with acute myeloid leukemia and FLT3-TKD mutations: a subanalysis from the RATIFY trial.

Data de publicació: 13/10/2020

Autors de IIS La Fe

Miguel Ángel Sanz Alonso

Autor

Autors aliens a IIS La Fe

Voso MT
Larson RA
Jones D
Marcucci G
Prior T
Krauter J
Heuser M
Lavorgna S
Nomdedeu J
Geyer SM
Walker A
Wei AH
Sierra J
Brandwein JM
de Witte TM
Jansen JH
Niederwieser D
Appelbaum FR
Medeiros BC
Tallman MS
Schlenk RF
Ganser A
Amadori S
Cheng Y
Chen Y
Pallaud C
Du L
Piciocchi A
Ehninger G
Byrd J
Thiede C
Döhner K
Stone RM
Döhner H
Bloomfield CD
Lo-Coco F

Grups d'Investigació

Hematología y Hemoterapia

Investigador Principal

Javier De La Rubia Comos

Abstract

The results from the RATIFY trial (ClinicalTrials.gov: NCT00651261; CALGB 10603) showed that midostaurin combined with standard chemotherapy significantly improved outcomes in patients with FMS-like tyrosine kinase 3 (FLT3)-mutated acute myeloid leukemia (AML), compared with placebo. In this post hoc subgroup analysis from the trial, we evaluated the impact of midostaurin in 163 patients with FLT3-tyrosine kinase domain (TKD) mutations. At a median follow-up of 60.7 months (95% CI, 55.0-70.8), the 5-year event-free survival (EFS) rate was significantly higher in patients treated with midostaurin than in those treated with placebo (45.2% vs 30.1%; P = .044). A trend toward improved disease-free survival was also observed with midostaurin (67.3% vs 53.4%; P = .089), whereas overall survival (OS) was similar in the 2 groups. Patients with AML and NPM1mut/FLT3-TKDmut or core binding factor (CBF)-rearranged/FLT3-TKDmut genotypes had significantly prolonged OS with or without censoring at hematopoietic cell transplantation (HCT), compared with NPM1WT/CBF-negative AMLs. The multivariable model for OS and EFS adjusted for allogeneic HCT in first complete remission as a time-dependent covariable, revealed NPM1 mutations and CBF rearrangements as significant favorable factors. These data show that NPM1 mutations or CBF rearrangements identify favorable prognostic groups in patients with FLT3-TKD AMLs, independent of other factors, also in the context of midostaurin treatment.

Dades de la publicació

ISSN/ISSNe:: 2473-9529, 2473-9537
Tipus:: Article
Pàgines:: 4945-4954
DOI:: 10.1182/bloodadvances.2020002904
PubMed:: 33049054
Factor d'Impacte:: 2,685 SCImago ℠
Quartil:: Q1 SCImago ℠

Documents

No hi ha documents

Mètriques

Filiacions

Voso MT:: Department of Biomedicine and Prevention, University Tor Vergata, Rome, Italy
Larson RA:: Department of Medicine, University of Chicago, Chicago, IL
Krauter J:: Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Medical School, Hannover, Germany

Department of Hematology and Oncology, Klinikum Braunschweig, Braunschweig, Germany
Heuser M:: Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Medical School, Hannover, Germany
Lavorgna S:: Department of Biomedicine and Prevention, University Tor Vergata, Rome, Italy
Nomdedeu J:: Hematology Department, Hospital de la Santa Creu I Sant Pau and José Carreras Leukemia Research Institute, Autonomous University of Barcelona, Barcelona, Spain
Wei AH:: Department of Clinical Hematology, Alfred Hospital and Monash University, Melbourne, Australia
Sierra J:: Hematology Department, Hospital de la Santa Creu I Sant Pau and José Carreras Leukemia Research Institute, Autonomous University of Barcelona, Barcelona, Spain
Sanz MA:: Department of Hematology, Hospital Universitari i Politecnic La Fe, University of Valencia, Valencia, Spain

Centro de Investigación Biomédica en Red de Cáncer, Instituto Carlos III, Madrid, Spain
Brandwein JM:: Department of Medicine, University of Alberta, Edmonton, Canada
Niederwieser D:: Department of Hematology, University of Leipzig, Leipzig, Germany
Appelbaum FR:: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA
Schlenk RF:: Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany

Department of Internal Medicine V, Heidelberg University Hospital, Heidelberg, Germany

NCT Trial Center, German Cancer Research Center, Heidelberg, Germany
Ganser A:: Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Medical School, Hannover, Germany
Amadori S:: Department of Biomedicine and Prevention, University Tor Vergata, Rome, Italy
Pallaud C:: Novaremed AG, Basel, Switzerland
Piciocchi A:: GIMEMA Data Center, Rome, Italy
Ehninger G:: Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus der TU Dresden, Dresden, Germany

and
Thiede C:: Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus der TU Dresden, Dresden, Germany

and
Döhner K:: Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany
Döhner H:: Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany
Lo-Coco F:: Department of Biomedicine and Prevention, University Tor Vergata, Rome, Italy

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