Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Jun 22:11:41-54.
doi: 10.2147/BLCTT.S236446. eCollection 2021.

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   3   4 , Yishai Ofran  2   4
Affiliations
Review

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

Galia Stemer et al. Blood Lymphat Cancer. .

Abstract

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: acute myeloid leukemia; ivosidenib; mutant IDH1.

PubMed Disclaimer

Conflict of interest statement

The authors declare no potential conflicts of interest.

Figures

Figure 1
Figure 1
How to incorporate ivosidenib in AML treatment.
See this image and copyright information in PMC

References

    1. Döhner H, Estey E, Grimwade D, et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017;129(4):424–447. - PMC - PubMed
    1. DiNardo CD, Jabbour E, Ravandi F, et al. IDH1 and IDH2 mutations in myelodysplastic syndromes and role in disease progression. Leukemia. 2016;30(4):980–984. doi:10.1038/leu.2015.211 - DOI - PMC - PubMed
    1. Rowe JM. Progress and predictions: AML in 2018. Best Pract Res Clin Haematol. 2018;31(4):337–340. doi:10.1016/j.beha.2018.09.002 - DOI - PubMed
    1. Mardis ER, Ding L, Dooling DJ, et al. Recurring mutations found by sequencing an acute myeloid leukemia genome. N Engl J Med. 2009;361(11):1058–1066. doi:10.1056/NEJMoa0903840 - DOI - PMC - PubMed
    1. Donker ML, Ossenkoppele GJ. Evaluating ivosidenib for the treatment of acute myeloid leukemia. Expert Opin Pharmacother. 2020;1–9. - PubMed