Midostaurin reduces relapse in FLT3-mutant acute myeloid leukemia: the Alliance CALGB 10603/RATIFY trial.

Fecha de publicación: 02/03/2021 Fecha Ahead of Print: 02/03/2021

Autores de IIS La Fe

Miguel Ángel Sanz Alonso

Autor

Participantes ajenos a IIS La Fe

Larson RA
Mandrekar SJ
Huebner LJ
Sanford BL
Laumann K
Geyer S
Bloomfield CD
Thiede C
Prior TW
Döhner K
Marcucci G
Voso MT
Klisovic RB
Galinsky I
Wei AH
Sierra J
Brandwein JM
de Witte T
Niederwieser D
Appelbaum FR
Medeiros BC
Tallman MS
Krauter J
Schlenk RF
Ganser A
Serve H
Ehninger G
Amadori S
Gathmann I
Döhner H
Stone RM

Grupos

Hematología y Hemoterapia

Investigador Principal

Javier De La Rubia Comos

Abstract

The prospective randomized, placebo-controlled CALGB 10603/RATIFY trial (Alliance) demonstrated a statistically significant overall survival benefit from the addition of midostaurin to standard frontline chemotherapy in a genotypically-defined subgroup of 717 patients with FLT3-mutant acute myeloid leukemia (AML). The risk of death was reduced by 22% on the midostaurin-containing arm. In this post hoc analysis, we analyzed the cumulative incidence of relapse (CIR) on this study and also evaluated the impact of 12 4-week cycles of maintenance therapy. CIR analyses treated relapses and AML deaths as events, deaths from other causes as competing risks, and survivors in remission were censored. CIR was improved on the midostaurin arm (HR = 0.71 (95% CI, 0.54-0.93); p = 0.01), both overall and within European LeukemiaNet 2017 risk classification subsets when post-transplant events were considered in the analysis as events. However, when transplantation was considered as a competing risk, there was overall no significant difference between the risks of relapse on the two randomized arms. Patients still in remission after consolidation with high-dose cytarabine entered the maintenance phase, continuing with either midostaurin or placebo. Analyses were inconclusive in quantifying the impact of the maintenance phase on the overall outcome. In summary, midostaurin reduces the CIR.

Datos de la publicación

ISSN/ISSNe:: 0887-6924, 1476-5551
Tipo:: Article
Páginas:: 2539-2551
DOI:: 10.1038/s41375-021-01179-4
Factor de Impacto:: 4,030 SCImago ℠
Cuartil:: Q1 SCImago ℠

Documentos

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Métricas

Filiaciones

Larson RA:: Department of Medicine and Comprehensive Cancer Center, University of Chicago, Chicago, IL, USA.
Mandrekar SJ:: Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA

Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN, USA
Huebner LJ:: Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN, USA
Sanford BL:: Alliance Statistics and Data Center, Duke University, Durham, NC, USA
Laumann K:: Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN, USA
Geyer S:: Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN, USA
Bloomfield CD:: The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA
Thiede C:: Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus der TU Dresden, Dresden, Germany
Prior TW:: The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA
Döhner K:: Department of Internal Medicine III, University of Ulm, Ulm, Germany
Marcucci G:: City of Hope Comprehensive Cancer Center, Duarte, CA, USA
Voso MT:: Department of Biomedicine and Prevention, University Tor Vergata, Rome, Italy
Klisovic RB:: Emory University School of Medicine, Atlanta, GA, USA
Galinsky I:: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
Wei AH:: Department of Clinical Haematology, The Alfred Hospital and Monash University, Melbourne, Australia
Sierra J:: Hematology Department, Hospital de la Santa Creu i Sant Pau, IIB Sant Pau and Jose Carreras Leukemia Research Institute, Autonomous University of Barcelona, Barcelona, Spain
Sanz MA:: Department of Hematology, Hospital Universitario y Politécnico La Fe and Department of Medicine, University of Valencia, Valencia, Spain
Brandwein JM:: Department of Medicine, University of Alberta, Edmonton, AB, Canada
de Witte T:: Radboud University Medical Centre, Nijmegen, Netherlands
Niederwieser D:: Department of Hematology and Oncology, University of Leipzig, Leipzig, Germany
Appelbaum FR:: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
Medeiros BC:: Division of Hematology, Stanford Comprehensive Cancer Center, Stanford University, Stanford, CA, USA
Tallman MS:: Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
Krauter J:: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany
Schlenk RF:: Department of Internal Medicine III, University of Ulm, Ulm, Germany

NCT Trial Center, National Center of Tumor Diseases, Heidelberg University Hospital and German Cancer Research Center, Heidelberg, Germany
Ganser A:: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany
Serve H:: Department of Medicine II, Hematology/Oncology, Goethe University Hospital Frankfurt, Frankfurt/Main, Germany
Ehninger G:: Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus der TU Dresden, Dresden, Germany
Amadori S:: Department of Biomedicine and Prevention, University Tor Vergata, Rome, Italy
Gathmann I:: Novartis Pharma AG, Basel, Switzerland
Döhner H:: Department of Internal Medicine III, University of Ulm, Ulm, Germany
Stone RM:: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA

Campos de estudio

Proyectos asociados

RED DE INVESTIGACION COOPERATIVA DE CANCER

RD06/0020/0031 . INSTITUTO DE SALUD CARLOS III; FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA . 2006

PROYECTO CAIBER

CAI08/01/0061 . INSTITUTO DE SALUD CARLOS III; FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA . 2009

CREACION Y MEJORA DE INFRAESTRUCTURAS EN MEDICINA REGENERATIVA

Investigador Principal: FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA

PLE2009-0141 ACI-PLAN E . MINISTERIO DE CIENCIA E INNOVACION; FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA . 2009

EVALUACIÓN DE LAS ADHESIONES FOCALES COMO NUEVAS DIANAS TERAPÉUTICAS EN LEUCEMIA MIELOIDE AGUDA.

Investigador Principal: MIGUEL ÁNGEL SANZ ALONSO

2010_0190_MARATON_TV3_SANZ . FUNDACIÓ LA MARATÓ DE TV3 . 2010

CONTRATO POST FSE (RIO HORTEGA)

CM11/00343 . INSTITUTO DE SALUD CARLOS III; FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA . 2012

CARACTERIZACIÓN MOLECULAR DE FORMAS ESPECÍFICAS DE LEUCEMIA MIELOBLÁSTICA AGUDA (LMA) MEDIANTE SECUENCIACIÓN EXÓMICA COMPLETA

Investigador Principal: MIGUEL ÁNGEL SANZ ALONSO

PI12/01047 . INSTITUTO DE SALUD CARLOS III; FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA . 2013

RED TEMATICA DE INVESTIGACION COOPERATIVA EN CANCER (RTICC)

Investigador Principal: MIGUEL ÁNGEL SANZ ALONSO

RD12/0036/0014 . INSTITUTO DE SALUD CARLOS III . 2013

COMPREHENSIVE, INTEGRATIVE AND GENOMIC APPROACH TO THE UNDERSTANDING AND TREATMENT OF CANCER AND LEUKEMIA.

Investigador Principal: MIGUEL ÁNGEL SANZ ALONSO

PIE13/00046 . INSTITUTO DE SALUD CARLOS III; FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA . 2014

CARACTERIZACIÓN MOLECULAR DE LEUCEMIA MIELOBLÁSTICA AGUDA (LMA) MEDIANTE SECUENCIACIÓN EXÓMICA COMPLETA

2013_0327_CPR_POSTRESIDENTES_ALONSO . FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA . 2013

CON-CIENCIA-YV: PILDORAS DE SALUD

FCT-13-7457_FECYT_2013 . MINISTERIO DE ECONOMIA Y COMPETITIVIDAD; FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA . 2013