$IDH1-mutated relapsed or refractory AML: current challenges and future prospects$
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IDH1-mutated relapsed or refractory AML: current challenges and future prospects

Juan Eduardo Megías-Vericat,1 Octavio Ballesta-López,1 Eva Barragán,2,3 Pau Montesinos2,31Servicio de Farmacia, Área del Medicamento, Hospital Universitari i Politècnic La Fe, Valencia, Spain; 2Servicio de Hematología y Hemoterapia, H...

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Autores principales:	Megías-Vericat JE, Ballesta-López O, Barragán E, Montesinos P
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	IDH1 isocitrate dehydrogenase 1 acute myeloid leukemia relapsed/refractory ivosidenib FT-2102 venetoclax. Diseases of the blood and blood-forming organs RC633-647.5
Acceso en línea:	https://doaj.org/article/644517ea4c7d4750a7e0382dca92bc5f
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spelling	oai:doaj.org-article:644517ea4c7d4750a7e0382dca92bc5f2021-12-02T11:18:27ZIDH1-mutated relapsed or refractory AML: current challenges and future prospects1179-9889https://doaj.org/article/644517ea4c7d4750a7e0382dca92bc5f2019-06-01T00:00:00Zhttps://www.dovepress.com/idh1-mutated-relapsed-or-refractory-aml-current-challenges-and-future--peer-reviewed-article-BLCTThttps://doaj.org/toc/1179-9889Juan Eduardo Megías-Vericat,1 Octavio Ballesta-López,1 Eva Barragán,2,3 Pau Montesinos2,31Servicio de Farmacia, Área del Medicamento, Hospital Universitari i Politècnic La Fe, Valencia, Spain; 2Servicio de Hematología y Hemoterapia, Hospital Universitari i Politècnic La Fe, Valencia, Spain; 3CIBERONC, Instituto Carlos III, Madrid, SpainAbstract: The prognosis of patients with relapsed or refractory acute myeloid leukemia (R/R AML) is discouraging with salvage standard approaches. Mutations of isocitrate dehydrogenase 1 (IDH1mut,), present in 7–14% of AML patients, have been discovered recently, opening the door to targeted agents aiming to improve the outcomes in this setting. Several oral selective IDH1mut, inhibitors are under investigation, ivosidenib being the first approved for R/R AML. We performed a systematic review to analyze the clinical outcomes and safety reported with IDH1mut, inhibitors and other agents in adult patients with IDH1mut, R/R AML. Ivosidenib in monotherapy achieved complete remission (CR) of 24%, overall response of 42%, and median overall survival of 9 months in R/R AML, and promising outcomes were reported with IDH305 and FT-2102. IDH1mut, inhibitors were generally well tolerated, but some therapy-related toxicities should be monitored, including IDH-differentiation syndrome, prolongation of the QT interval, and leukocytosis, all manageable and reversible. Also, venetoclax, CB-839, PARP inhibitors, and IDH1 peptide vaccine are being studied in IDH1mut, AML. The results of the ongoing and upcoming clinical trials will bring new evidence to establish the role of IDH1mut, inhibitors in therapeutic strategies of AML.Keywords: isocitrate dehydrogenase 1, acute myeloid leukemia, relapsed/refractory, ivosidenib, FT-2102, venetoclaxMegías-Vericat JEBallesta-López OBarragán EMontesinos PDove Medical PressarticleIDH1isocitrate dehydrogenase 1acute myeloid leukemiarelapsed/refractoryivosidenibFT-2102venetoclax.Diseases of the blood and blood-forming organsRC633-647.5ENBlood and Lymphatic Cancer: Targets and Therapy, Vol Volume 9, Pp 19-32 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	IDH1 isocitrate dehydrogenase 1 acute myeloid leukemia relapsed/refractory ivosidenib FT-2102 venetoclax. Diseases of the blood and blood-forming organs RC633-647.5
spellingShingle	IDH1 isocitrate dehydrogenase 1 acute myeloid leukemia relapsed/refractory ivosidenib FT-2102 venetoclax. Diseases of the blood and blood-forming organs RC633-647.5 Megías-Vericat JE Ballesta-López O Barragán E Montesinos P IDH1-mutated relapsed or refractory AML: current challenges and future prospects
description	Juan Eduardo Megías-Vericat,1 Octavio Ballesta-López,1 Eva Barragán,2,3 Pau Montesinos2,31Servicio de Farmacia, Área del Medicamento, Hospital Universitari i Politècnic La Fe, Valencia, Spain; 2Servicio de Hematología y Hemoterapia, Hospital Universitari i Politècnic La Fe, Valencia, Spain; 3CIBERONC, Instituto Carlos III, Madrid, SpainAbstract: The prognosis of patients with relapsed or refractory acute myeloid leukemia (R/R AML) is discouraging with salvage standard approaches. Mutations of isocitrate dehydrogenase 1 (IDH1mut,), present in 7–14% of AML patients, have been discovered recently, opening the door to targeted agents aiming to improve the outcomes in this setting. Several oral selective IDH1mut, inhibitors are under investigation, ivosidenib being the first approved for R/R AML. We performed a systematic review to analyze the clinical outcomes and safety reported with IDH1mut, inhibitors and other agents in adult patients with IDH1mut, R/R AML. Ivosidenib in monotherapy achieved complete remission (CR) of 24%, overall response of 42%, and median overall survival of 9 months in R/R AML, and promising outcomes were reported with IDH305 and FT-2102. IDH1mut, inhibitors were generally well tolerated, but some therapy-related toxicities should be monitored, including IDH-differentiation syndrome, prolongation of the QT interval, and leukocytosis, all manageable and reversible. Also, venetoclax, CB-839, PARP inhibitors, and IDH1 peptide vaccine are being studied in IDH1mut, AML. The results of the ongoing and upcoming clinical trials will bring new evidence to establish the role of IDH1mut, inhibitors in therapeutic strategies of AML.Keywords: isocitrate dehydrogenase 1, acute myeloid leukemia, relapsed/refractory, ivosidenib, FT-2102, venetoclax
format	article
author	Megías-Vericat JE Ballesta-López O Barragán E Montesinos P
author_facet	Megías-Vericat JE Ballesta-López O Barragán E Montesinos P
author_sort	Megías-Vericat JE
title	IDH1-mutated relapsed or refractory AML: current challenges and future prospects
title_short	IDH1-mutated relapsed or refractory AML: current challenges and future prospects
title_full	IDH1-mutated relapsed or refractory AML: current challenges and future prospects
title_fullStr	IDH1-mutated relapsed or refractory AML: current challenges and future prospects
title_full_unstemmed	IDH1-mutated relapsed or refractory AML: current challenges and future prospects
title_sort	idh1-mutated relapsed or refractory aml: current challenges and future prospects
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/644517ea4c7d4750a7e0382dca92bc5f
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IDH1-mutated relapsed or refractory AML: current challenges and future prospects

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