Impact of FLT3-ITD Mutation Status and Its Ratio in a Cohort of 2901 Patients Undergoing Upfront Intensive Chemotherapy: A PETHEMA Registry Study.

FLT3-ITD results in a poor prognosis in terms of overall survival (OS) and relapse-free survival (RFS) in acute myeloid leukemia (AML). However, the prognostic usefulness of the allelic ratio (AR) to select post-remission therapy remains controversial. Our study focuses on the prognostic impact of F...

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Autores: Ayala, R, Carreno-Tarragona, G, Barragan, E, Boluda, B, Larrayoz, MJ, Chillon, MC, Carrillo-Cruz, E, Bilbao, C, Sanchez-Garcia, J, Bernal, T, Martinez-Cuadron, D, Gil, C, Serrano, J, Rodriguez-Medina, C, Bergua, J, Perez-Simon, JA, Calbacho, M, Alonso-Dominguez, JM, Labrador, J, Tormo, M, Amigo, ML, Herrera-Puente, P, Rapado, I, Sargas, C, Vazquez, I, Calasanz, MJ, Gomez-Casares, T, Garcia-Sanz, R, Sanz, MA, Martinez-Lopez, J, Montesinos, P
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:INCLIVA
Repositorio:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
OAI Identifier:oai:incliva.fundanetsuite.com:p17144
Acceso en línea:https://incliva.portalinvestigacion.com/publicaciones/17144
Access Level:acceso abierto
Palabra clave:FLT3–ITD mutation and ratio
acute myeloid leukemia (AML)
death
outcome
prognosis
real-world outcomes
relapse
survival
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spelling Impact of FLT3-ITD Mutation Status and Its Ratio in a Cohort of 2901 Patients Undergoing Upfront Intensive Chemotherapy: A PETHEMA Registry Study.Ayala, RCarreno-Tarragona, GBarragan, EBoluda, BLarrayoz, MJChillon, MCCarrillo-Cruz, EBilbao, CSanchez-Garcia, JBernal, TMartinez-Cuadron, DGil, CSerrano, JRodriguez-Medina, CBergua, JPerez-Simon, JACalbacho, MAlonso-Dominguez, JMLabrador, JTormo, MAmigo, MLHerrera-Puente, PRapado, ISargas, CVazquez, ICalasanz, MJGomez-Casares, TGarcia-Sanz, RSanz, MAMartinez-Lopez, JMontesinos, PFLT3–ITD mutation and ratioacute myeloid leukemia (AML)deathoutcomeprognosisreal-world outcomesrelapsesurvivalFLT3-ITD results in a poor prognosis in terms of overall survival (OS) and relapse-free survival (RFS) in acute myeloid leukemia (AML). However, the prognostic usefulness of the allelic ratio (AR) to select post-remission therapy remains controversial. Our study focuses on the prognostic impact of FLT3-ITD and its ratio in a series of 2901 adult patients treated intensively in the pre-FLT3 inhibitor era and reported in the PETHEMA registry. A total of 579 of these patients (20%) harbored FLT3-ITD mutations. In multivariate analyses, patients with an FLT3-ITD allele ratio (AR) of >0.5 showed a lower complete remission (CR rate) and OS (HR 1.47, p = 0.009), while AR > 0.8 was associated with poorer RFS (HR 2.1; p < 0.001). Among NPM1/FLT3-ITD-mutated patients, median OS gradually decreased according to FLT3-ITD status and ratio (34.3 months FLT3-ITD-negative, 25.3 months up to 0.25, 14.5 months up to 0.5, and 10 months = 0.5, p < 0.001). Post-remission allogeneic transplant (allo-HSCT) resulted in better OS and RFS as compared to auto-HSCT in NPM1/FLT3-ITD-mutated AML regardless of pre-established AR cutoff (=0.5 vs. >0.5). Using the maximally selected log-rank statistics, we established an optimal cutoff of FLT3-ITD AR of 0.44 for OS, and 0.8 for RFS. We analyzed the OS and RFS according to FLT3-ITD status in all patients, and we found that the group of FLT3-ITD-positive patients with AR < 0.44 had similar 5-year OS after allo-HSCT or auto-HSCT (52% and 41%, respectively, p = 0.86), but worse RFS after auto-HSCT (p = 0.01). Among patients with FLT3-ITD AR > 0.44, allo-HSCT was superior to auto-HSCT in terms of OS and RFS. This study provides more evidence for a better characterization of patients with AML harboring FLT3-ITD mutations.MDPI2022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://incliva.portalinvestigacion.com/publicaciones/17144CancersISSN: 20726694reponame:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVAinstname:INCLIVAInglésinfo:eu-repo/semantics/openAccessoai:incliva.fundanetsuite.com:p171442026-06-07T16:35:31Z
dc.title.none.fl_str_mv Impact of FLT3-ITD Mutation Status and Its Ratio in a Cohort of 2901 Patients Undergoing Upfront Intensive Chemotherapy: A PETHEMA Registry Study.
title Impact of FLT3-ITD Mutation Status and Its Ratio in a Cohort of 2901 Patients Undergoing Upfront Intensive Chemotherapy: A PETHEMA Registry Study.
spellingShingle Impact of FLT3-ITD Mutation Status and Its Ratio in a Cohort of 2901 Patients Undergoing Upfront Intensive Chemotherapy: A PETHEMA Registry Study.
Ayala, R
FLT3–ITD mutation and ratio
acute myeloid leukemia (AML)
death
outcome
prognosis
real-world outcomes
relapse
survival
title_short Impact of FLT3-ITD Mutation Status and Its Ratio in a Cohort of 2901 Patients Undergoing Upfront Intensive Chemotherapy: A PETHEMA Registry Study.
title_full Impact of FLT3-ITD Mutation Status and Its Ratio in a Cohort of 2901 Patients Undergoing Upfront Intensive Chemotherapy: A PETHEMA Registry Study.
title_fullStr Impact of FLT3-ITD Mutation Status and Its Ratio in a Cohort of 2901 Patients Undergoing Upfront Intensive Chemotherapy: A PETHEMA Registry Study.
title_full_unstemmed Impact of FLT3-ITD Mutation Status and Its Ratio in a Cohort of 2901 Patients Undergoing Upfront Intensive Chemotherapy: A PETHEMA Registry Study.
title_sort Impact of FLT3-ITD Mutation Status and Its Ratio in a Cohort of 2901 Patients Undergoing Upfront Intensive Chemotherapy: A PETHEMA Registry Study.
dc.creator.none.fl_str_mv Ayala, R
Carreno-Tarragona, G
Barragan, E
Boluda, B
Larrayoz, MJ
Chillon, MC
Carrillo-Cruz, E
Bilbao, C
Sanchez-Garcia, J
Bernal, T
Martinez-Cuadron, D
Gil, C
Serrano, J
Rodriguez-Medina, C
Bergua, J
Perez-Simon, JA
Calbacho, M
Alonso-Dominguez, JM
Labrador, J
Tormo, M
Amigo, ML
Herrera-Puente, P
Rapado, I
Sargas, C
Vazquez, I
Calasanz, MJ
Gomez-Casares, T
Garcia-Sanz, R
Sanz, MA
Martinez-Lopez, J
Montesinos, P
author Ayala, R
author_facet Ayala, R
Carreno-Tarragona, G
Barragan, E
Boluda, B
Larrayoz, MJ
Chillon, MC
Carrillo-Cruz, E
Bilbao, C
Sanchez-Garcia, J
Bernal, T
Martinez-Cuadron, D
Gil, C
Serrano, J
Rodriguez-Medina, C
Bergua, J
Perez-Simon, JA
Calbacho, M
Alonso-Dominguez, JM
Labrador, J
Tormo, M
Amigo, ML
Herrera-Puente, P
Rapado, I
Sargas, C
Vazquez, I
Calasanz, MJ
Gomez-Casares, T
Garcia-Sanz, R
Sanz, MA
Martinez-Lopez, J
Montesinos, P
author_role author
author2 Carreno-Tarragona, G
Barragan, E
Boluda, B
Larrayoz, MJ
Chillon, MC
Carrillo-Cruz, E
Bilbao, C
Sanchez-Garcia, J
Bernal, T
Martinez-Cuadron, D
Gil, C
Serrano, J
Rodriguez-Medina, C
Bergua, J
Perez-Simon, JA
Calbacho, M
Alonso-Dominguez, JM
Labrador, J
Tormo, M
Amigo, ML
Herrera-Puente, P
Rapado, I
Sargas, C
Vazquez, I
Calasanz, MJ
Gomez-Casares, T
Garcia-Sanz, R
Sanz, MA
Martinez-Lopez, J
Montesinos, P
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv FLT3–ITD mutation and ratio
acute myeloid leukemia (AML)
death
outcome
prognosis
real-world outcomes
relapse
survival
topic FLT3–ITD mutation and ratio
acute myeloid leukemia (AML)
death
outcome
prognosis
real-world outcomes
relapse
survival
description FLT3-ITD results in a poor prognosis in terms of overall survival (OS) and relapse-free survival (RFS) in acute myeloid leukemia (AML). However, the prognostic usefulness of the allelic ratio (AR) to select post-remission therapy remains controversial. Our study focuses on the prognostic impact of FLT3-ITD and its ratio in a series of 2901 adult patients treated intensively in the pre-FLT3 inhibitor era and reported in the PETHEMA registry. A total of 579 of these patients (20%) harbored FLT3-ITD mutations. In multivariate analyses, patients with an FLT3-ITD allele ratio (AR) of >0.5 showed a lower complete remission (CR rate) and OS (HR 1.47, p = 0.009), while AR > 0.8 was associated with poorer RFS (HR 2.1; p < 0.001). Among NPM1/FLT3-ITD-mutated patients, median OS gradually decreased according to FLT3-ITD status and ratio (34.3 months FLT3-ITD-negative, 25.3 months up to 0.25, 14.5 months up to 0.5, and 10 months = 0.5, p < 0.001). Post-remission allogeneic transplant (allo-HSCT) resulted in better OS and RFS as compared to auto-HSCT in NPM1/FLT3-ITD-mutated AML regardless of pre-established AR cutoff (=0.5 vs. >0.5). Using the maximally selected log-rank statistics, we established an optimal cutoff of FLT3-ITD AR of 0.44 for OS, and 0.8 for RFS. We analyzed the OS and RFS according to FLT3-ITD status in all patients, and we found that the group of FLT3-ITD-positive patients with AR < 0.44 had similar 5-year OS after allo-HSCT or auto-HSCT (52% and 41%, respectively, p = 0.86), but worse RFS after auto-HSCT (p = 0.01). Among patients with FLT3-ITD AR > 0.44, allo-HSCT was superior to auto-HSCT in terms of OS and RFS. This study provides more evidence for a better characterization of patients with AML harboring FLT3-ITD mutations.
publishDate 2022
dc.date.none.fl_str_mv 2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://incliva.portalinvestigacion.com/publicaciones/17144
url https://incliva.portalinvestigacion.com/publicaciones/17144
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv Cancers
ISSN: 20726694
reponame:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
instname:INCLIVA
instname_str INCLIVA
reponame_str r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
collection r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
repository.name.fl_str_mv
repository.mail.fl_str_mv
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