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Enasidenib in acute myeloid leukemia: clinical development and perspectives on treatment

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Title: Enasidenib in acute myeloid leukemia: clinical development and perspectives on treatment
Authors: Reed DR, Elsarrag RZ, Morris AL, Keng MK
Source: Cancer Management and Research, Vol Volume 11, Pp 8073-8080 (2019)
Publisher Information: Dove Medical Press, 2019.
Publication Year: 2019
Collection: LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Subject Terms: isocitrate dehydrogenase (IDH) 2, relapsed/refractory (R/R) acute myeloid leukemia (AML), enasidenib, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
More Details: Daniel R Reed,1 Ramey Z Elsarrag,2 Amy L Morris,3 Michael K Keng11Division of Hematology/Oncology, Department of Medicine, University of Virginia, Charlottesville, VA, USA; 2Department of Medicine, University of Virginia, Charlottesville, VA, USA; 3Department of Pharmacy Services, University of Virginia, Charlottesville, VA, USACorrespondence: Michael K KengDepartment of Medicine, Division of Hematology/Oncology, University of Virginia, 1300 Jefferson Park Avenue, West Complex, Room 6009, Charlottesville, VA 22908, USATel +1 434 924 4257Fax +1 434 244 7534Email MK2PV@virginia.eduAbstract: Recently there has been a significant progression in the understanding of molecular mutations driving biochemical and cellular signaling changes leading to survival and proliferation of leukemia cells in patients with acute myeloid leukemia (AML). Preclinical studies have demonstrated a mutated enzyme in the citric acid cycle, isocitrate dehydrogenase (IDH), leads to the production of an oncogenic metabolite R-2-hydroxy-glutarate (R-2-HG). This causes the arrest in the differentiation of hematopoietic stem cells leading to the promotion of leukemia. Inhibitors of the IDH enzyme have been shown in preclinical studies to reduce the production of R-2-HG, resulting in terminal differentiation of leukemia blast cells. In recent phase I and II trials, the IDH2 inhibitor enasidenib has shown clinical activity in patients with relapsed and refractory (R/R) AML. This review will describe the preclinical and clinical developments of enasidenib and its Food and Drug Administration approval in R/R AML, treatment recommendations and management will be outlined.Keywords: isocitrate dehydrogenase, IDH 2, relapsed/refractory, R/R acute myeloid leukemia AML, enasidenib, IDH, AML
Document Type: article
File Description: electronic resource
Language: English
ISSN: 1179-1322
Relation: https://www.dovepress.com/enasidenib-in-acute-myeloid-leukemia-clinical-development-and-perspect-peer-reviewed-article-CMAR; https://doaj.org/toc/1179-1322
Access URL: https://doaj.org/article/0ac22375ab1d46d98324f5388e457b03
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  Data: Daniel R Reed,1 Ramey Z Elsarrag,2 Amy L Morris,3 Michael K Keng11Division of Hematology/Oncology, Department of Medicine, University of Virginia, Charlottesville, VA, USA; 2Department of Medicine, University of Virginia, Charlottesville, VA, USA; 3Department of Pharmacy Services, University of Virginia, Charlottesville, VA, USACorrespondence: Michael K KengDepartment of Medicine, Division of Hematology/Oncology, University of Virginia, 1300 Jefferson Park Avenue, West Complex, Room 6009, Charlottesville, VA 22908, USATel +1 434 924 4257Fax +1 434 244 7534Email MK2PV@virginia.eduAbstract: Recently there has been a significant progression in the understanding of molecular mutations driving biochemical and cellular signaling changes leading to survival and proliferation of leukemia cells in patients with acute myeloid leukemia (AML). Preclinical studies have demonstrated a mutated enzyme in the citric acid cycle, isocitrate dehydrogenase (IDH), leads to the production of an oncogenic metabolite R-2-hydroxy-glutarate (R-2-HG). This causes the arrest in the differentiation of hematopoietic stem cells leading to the promotion of leukemia. Inhibitors of the IDH enzyme have been shown in preclinical studies to reduce the production of R-2-HG, resulting in terminal differentiation of leukemia blast cells. In recent phase I and II trials, the IDH2 inhibitor enasidenib has shown clinical activity in patients with relapsed and refractory (R/R) AML. This review will describe the preclinical and clinical developments of enasidenib and its Food and Drug Administration approval in R/R AML, treatment recommendations and management will be outlined.Keywords: isocitrate dehydrogenase, IDH 2, relapsed/refractory, R/R acute myeloid leukemia AML, enasidenib, IDH, AML
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      – SubjectFull: isocitrate dehydrogenase (IDH) 2
        Type: general
      – SubjectFull: relapsed/refractory (R/R) acute myeloid leukemia (AML)
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