Efficacy and Safety Profile of Ivosidenib in the Management of Patients with Acute Myeloid Leukemia (AML): An Update on the Emerging Evidence

Galia Stemer,1 Jacob M Rowe,2– 4 Yishai Ofran2,4 1Institute of Hematology, Ha’Emek Medical Center, Afula, Israel; 2Department of Hematology and Bone Marrow Transplantation, Rambam Health Care Campus, Haifa, Israel; 3Department of Hematology, Shaare Zedek Medical Center, Jerusalem...

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Autores principales:	Stemer G, Rowe JM, Ofran Y
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	mutant idh1 acute myeloid leukemia ivosidenib Diseases of the blood and blood-forming organs RC633-647.5
Acceso en línea:	https://doaj.org/article/c5b5aacb1fa546c1b7c4b95517c9ddd0
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spelling	oai:doaj.org-article:c5b5aacb1fa546c1b7c4b95517c9ddd02021-12-02T17:07:12ZEfficacy and Safety Profile of Ivosidenib in the Management of Patients with Acute Myeloid Leukemia (AML): An Update on the Emerging Evidence1179-9889https://doaj.org/article/c5b5aacb1fa546c1b7c4b95517c9ddd02021-06-01T00:00:00Zhttps://www.dovepress.com/efficacy-and-safety-profile-of-ivosidenib-in-the-management-of-patient-peer-reviewed-fulltext-article-BLCTThttps://doaj.org/toc/1179-9889Galia Stemer,1 Jacob M Rowe,2– 4 Yishai Ofran2,4 1Institute of Hematology, Ha’Emek Medical Center, Afula, Israel; 2Department of Hematology and Bone Marrow Transplantation, Rambam Health Care Campus, Haifa, Israel; 3Department of Hematology, Shaare Zedek Medical Center, Jerusalem, Israel; 4The Ruth and Bruce Rappaport Faculty of Medicine, Technion, Haifa, IsraelCorrespondence: Jacob M RoweDepartment of Hematology, Shaare Zedek Medical Center, Shmu’el Bait St 12, Jerusalem, 91031, IsraelTel +972-2-6555204Fax +972-2-6555755Email rowe@rambam.health.gov.ilAbstract: The isocitrate dehydrogenase enzyme, catalyzing isocitrate conversion to α-ketoglutarate (αKG) in both the cell cytoplasm and mitochondria, contributes to the production of dihydronicotinamide-adenine dinucleotide phosphate (NADPH) as a reductive potential in various cellular processes. IDH1 gene mutations are revealed in up to 20% of the patients with acute myeloid leukemia (AML). A mutant IDH enzyme, existing in the cell cytoplasm and possessing neomorphic activity, converts αKG into oncometabolite R-2-hydroxyglutarate (R-2-HG) that accumulates in high amounts in the cell and inhibits αKG-dependent enzymes, including epigenetic regulators. The resultant alteration in gene expression and blockade of differentiation ultimately lead to leukemia development. Myeloid differentiation capacity can be restored by obstruction of the mutant enzyme, inducing substantial reduction in R-2-HG levels. Ivosidenib, a potent selective inhibitor of mutant IDH1, is a differentiating agent shown to be clinically effective in newly diagnosed AML (ND-AML) and relapsed/refractory (R/R) AML harboring this mutation. The drug is approved by the Food and Drug Administration (FDA) as a single-agent treatment for R/R AML. Significance of mutated IDH1 targeting and a potential role of ivosidenib in AML management, when used either as a single agent or as part of combination therapies, will be reviewed herein.Keywords: mutant IDH1, acute myeloid leukemia, ivosidenibStemer GRowe JMOfran YDove Medical Pressarticlemutant idh1acute myeloid leukemiaivosidenibDiseases of the blood and blood-forming organsRC633-647.5ENBlood and Lymphatic Cancer: Targets and Therapy, Vol Volume 11, Pp 41-54 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	mutant idh1 acute myeloid leukemia ivosidenib Diseases of the blood and blood-forming organs RC633-647.5
spellingShingle	mutant idh1 acute myeloid leukemia ivosidenib Diseases of the blood and blood-forming organs RC633-647.5 Stemer G Rowe JM Ofran Y Efficacy and Safety Profile of Ivosidenib in the Management of Patients with Acute Myeloid Leukemia (AML): An Update on the Emerging Evidence
description	Galia Stemer,1 Jacob M Rowe,2– 4 Yishai Ofran2,4 1Institute of Hematology, Ha’Emek Medical Center, Afula, Israel; 2Department of Hematology and Bone Marrow Transplantation, Rambam Health Care Campus, Haifa, Israel; 3Department of Hematology, Shaare Zedek Medical Center, Jerusalem, Israel; 4The Ruth and Bruce Rappaport Faculty of Medicine, Technion, Haifa, IsraelCorrespondence: Jacob M RoweDepartment of Hematology, Shaare Zedek Medical Center, Shmu’el Bait St 12, Jerusalem, 91031, IsraelTel +972-2-6555204Fax +972-2-6555755Email rowe@rambam.health.gov.ilAbstract: The isocitrate dehydrogenase enzyme, catalyzing isocitrate conversion to α-ketoglutarate (αKG) in both the cell cytoplasm and mitochondria, contributes to the production of dihydronicotinamide-adenine dinucleotide phosphate (NADPH) as a reductive potential in various cellular processes. IDH1 gene mutations are revealed in up to 20% of the patients with acute myeloid leukemia (AML). A mutant IDH enzyme, existing in the cell cytoplasm and possessing neomorphic activity, converts αKG into oncometabolite R-2-hydroxyglutarate (R-2-HG) that accumulates in high amounts in the cell and inhibits αKG-dependent enzymes, including epigenetic regulators. The resultant alteration in gene expression and blockade of differentiation ultimately lead to leukemia development. Myeloid differentiation capacity can be restored by obstruction of the mutant enzyme, inducing substantial reduction in R-2-HG levels. Ivosidenib, a potent selective inhibitor of mutant IDH1, is a differentiating agent shown to be clinically effective in newly diagnosed AML (ND-AML) and relapsed/refractory (R/R) AML harboring this mutation. The drug is approved by the Food and Drug Administration (FDA) as a single-agent treatment for R/R AML. Significance of mutated IDH1 targeting and a potential role of ivosidenib in AML management, when used either as a single agent or as part of combination therapies, will be reviewed herein.Keywords: mutant IDH1, acute myeloid leukemia, ivosidenib
format	article
author	Stemer G Rowe JM Ofran Y
author_facet	Stemer G Rowe JM Ofran Y
author_sort	Stemer G
title	Efficacy and Safety Profile of Ivosidenib in the Management of Patients with Acute Myeloid Leukemia (AML): An Update on the Emerging Evidence
title_short	Efficacy and Safety Profile of Ivosidenib in the Management of Patients with Acute Myeloid Leukemia (AML): An Update on the Emerging Evidence
title_full	Efficacy and Safety Profile of Ivosidenib in the Management of Patients with Acute Myeloid Leukemia (AML): An Update on the Emerging Evidence
title_fullStr	Efficacy and Safety Profile of Ivosidenib in the Management of Patients with Acute Myeloid Leukemia (AML): An Update on the Emerging Evidence
title_full_unstemmed	Efficacy and Safety Profile of Ivosidenib in the Management of Patients with Acute Myeloid Leukemia (AML): An Update on the Emerging Evidence
title_sort	efficacy and safety profile of ivosidenib in the management of patients with acute myeloid leukemia (aml): an update on the emerging evidence
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/c5b5aacb1fa546c1b7c4b95517c9ddd0
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Efficacy and Safety Profile of Ivosidenib in the Management of Patients with Acute Myeloid Leukemia (AML): An Update on the Emerging Evidence

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