Back to Journals » Cancer Management and Research » Volume 11

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

Authors Reed DR, Elsarrag RZ, Morris AL, Keng MK

Received 13 May 2019

Accepted for publication 30 July 2019

Published 30 August 2019 Volume 2019:11 Pages 8073—8080

DOI https://doi.org/10.2147/CMAR.S162784

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 2

Editor who approved publication: Professor Bilikere Dwarakanath


Daniel R Reed,1 Ramey Z Elsarrag,2 Amy L Morris,3 Michael K Keng1

1Division 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, USA

Correspondence: Michael K Keng
Department of Medicine, Division of Hematology/Oncology, University of Virginia, 1300 Jefferson Park Avenue, West Complex, Room 6009, Charlottesville, VA 22908, USA
Tel +1 434 924 4257
Fax +1 434 244 7534
Email MK2PV@virginia.edu

Abstract: 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


Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]