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
. 2019 Jun 27:9:19-32.
doi: 10.2147/BLCTT.S177913. eCollection 2019.

IDH1-mutated relapsed or refractory AML: current challenges and future prospects

Juan Eduardo Megías-Vericat  1 , Octavio Ballesta-López  1 , Eva Barragán  2   3 , Pau Montesinos  2   3
Affiliations
Review

IDH1-mutated relapsed or refractory AML: current challenges and future prospects

Juan Eduardo Megías-Vericat et al. Blood Lymphat Cancer. .

Abstract

The prognosis of patients with relapsed or refractory acute myeloid leukemia (R/R AML) is discouraging with salvage standard approaches. Mutations of isocitrate dehydrogenase 1 (IDH1 mut ), present in 7-14% of AML patients, have been discovered recently, opening the door to targeted agents aiming to improve the outcomes in this setting. Several oral selective IDH1 mut inhibitors are under investigation, ivosidenib being the first approved for R/R AML. We performed a systematic review to analyze the clinical outcomes and safety reported with IDH1 mut inhibitors and other agents in adult patients with IDH1 mut R/R AML. Ivosidenib in monotherapy achieved complete remission (CR) of 24%, overall response of 42%, and median overall survival of 9 months in R/R AML, and promising outcomes were reported with IDH305 and FT-2102. IDH1 mut inhibitors were generally well tolerated, but some therapy-related toxicities should be monitored, including IDH-differentiation syndrome, prolongation of the QT interval, and leukocytosis, all manageable and reversible. Also, venetoclax, CB-839, PARP inhibitors, and IDH1 peptide vaccine are being studied in IDH1mut AML. The results of the ongoing and upcoming clinical trials will bring new evidence to establish the role of IDH1 mut inhibitors in therapeutic strategies of AML.

Keywords: FT-2102; acute myeloid leukemia; isocitrate dehydrogenase 1; ivosidenib; relapsed/refractory; venetoclax.

PubMed Disclaimer

Conflict of interest statement

Dr Pau Montesinos reports grants from Celgene and Daiichi Sankyo during the conduct of the study and is on the advisory board for AGIOS, Celgene and Daiichi Sankyo. The authors report no other conflicts of interest in this work.

Figures

Figure 1
Figure 1
Summary of evidence search and selection. Abbreviations: AML, acute myeloid leukemia; IDH1, isocitrate dehydrogenase 1; IDH2, isocitrate dehydrogenase 2; IDH1mut, isocitrate dehydrogenase 1 mutated.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

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):424–427. doi:10.1182/blood-2016-08-733196 - DOI - PMC - PubMed
    1. Megias-Vericat JE, Martinez-Cuadron D, Sanz MA, Montesinos P. Salvage regimens using conventional chemotherapy agents for relapsed/refractory adult AML patients: a systematic literature review. Ann Hematol. 2018;97(7):1115–1153. doi:10.1007/s00277-018-3304-y - DOI - PubMed
    1. DiNardo CD, Ravandi F, Agresta S, et al. Characteristics, clinical outcome, and prognostic significance of IDH mutations in AML. Am J Hematol. 2015;90(8):732–736. doi:10.1002/ajh.24072 - DOI - PMC - PubMed
    1. Bertoli S, Tavitian S, Delabesse E, Sarry A, Huguet F, Récher C. Outcome of AML patients with IDH1 or IDH2 mutations from diagnosis and refractory/relapse phase of the disease in routine practice. Blood. 2016;128(22):1718. doi:10.1182/blood-2016-06-724161 - DOI
    1. Dhillon S. Ivosidenib: first Global Approval. Drugs. 2018;78(14):1509–1516. doi:10.1007/s40265-018-0978-3 - DOI - PMC - PubMed