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

被引：13

作者：

Reed, Daniel R. ^{[1
]}

Elsarrag, Ramey Z. ^{[2
]}

Morris, Amy L. ^{[3
]}

Keng, Michael K. ^{[1
]}

机构：

[1] Univ Virginia, Dept Med, Div Hematol Oncol, 1300 Jefferson Pk Ave,West Complex,Room 6009, Charlottesville, VA 22908 USA

[2] Univ Virginia, Dept Med, Charlottesville, VA 22908 USA

[3] Univ Virginia, Dept Pharm Serv, Charlottesville, VA 22908 USA

来源：

CANCER MANAGEMENT AND RESEARCH | 2019年 / 11卷

关键词：

isocitrate dehydrogenase; IDH; 2; relapsed/refractory; R/R acute myeloid leukemia AML; enasidenib; AML; MUTANT IDH2; MUTATIONS; 2-HYDROXYGLUTARATE;

D O I：

10.2147/CMAR.S162784

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：8073 / 8080

页数：8

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