Drugs & Therapy Perspectives

, Volume 35, Issue 4, pp 160–166 | Cite as

Ivosidenib in relapsed or refractory acute myeloid leukemia: a profile of its use in the USA

  • Emma H. McCafferty
  • Katherine A. Lyseng-WilliamsonEmail author
Adis Drug Q&A


Ivosidenib (Tibsovo®), a first-in-class, small molecule inhibitor of mutant isocitrate dehydrogenase 1 (IDH1), is an important new therapeutic option in the USA for treating adults with relapsed or refractory acute myeloid leukemia who have a susceptible IDH1 gene mutation. In such patients, oral ivosidenib is effective and generally well tolerated, producing encouraging rates and durations of complete remission (CR), CR or CR with partial hematologic recovery (CR/CRh), overall response, and overall survival. CR/CRh rates are consistent across most baseline characteristics. Ivosidenib also provides additional clinical benefits, including transfusion independence, improvements in hematologic variables, and deep molecular responses as measured by IDH1 mutation clearance in patients who achieve CR/CRh.



The manuscript was reviewed by: G. N. Mannis, Hematology/Blood and Marrow Transplant, Department of Medicine, University of California, San Francisco, CA, USA; A. S. Mims, Division of Hematology, Department of Medicine, Ohio State University, Columbus, OH, USA. During the peer review process, Agios Inc., the marketing-authorization holder of ivosidenib (Tibsovo®), was also offered an opportunity to provide a scientific accuracy review of their data. Changes resulting from comments received were made on the basis of scientific and editorial merit.

Compliance with ethical standards


The preparation of this review was not supported by any external funding.

Conflicts of interest

E.H. McCafferty and K.A. Lyseng-Williamson are employees of Adis/Springer, are responsible for the article content and declare no conflicts of interest.


  1. 1.
    National Comprehensive Cancer Network®. NCCN clinical practice guidelines in oncology (NCCN guidelines®): acute myeloid leukemia (version 3.2018). Plymouth Meeting, PA: National Comprehensive Cancer Network®, Inc.; 2018.Google Scholar
  2. 2.
    Frohling S, Scholl C, Gilliland DG, et al. Genetics of myeloid malignancies: pathogenetic and clinical implications. J Clin Oncol. 2005;23(26):6285–95.CrossRefGoogle Scholar
  3. 3.
    Marcucci G, Haferlach T, Dohner H. Molecular genetics of adult acute myeloid leukemia: prognostic and therapeutic implications. J Clin Oncol. 2011;29(5):475–86.CrossRefGoogle Scholar
  4. 4.
    Wouters BJ, Delwel R. Epigenetics and approaches to targeted epigenetic therapy in acute myeloid leukemia. Blood. 2016;127(1):42–52.CrossRefGoogle Scholar
  5. 5.
    Schoch C, Haferlach T. Cytogenetics in acute myeloid leukemia. Curr Oncol Rep. 2002;4(5):390–7.CrossRefGoogle Scholar
  6. 6.
    National Cancer Institute: Surveillance, epidemiology, and End Results Program (SEER). Cancer stat facts: leukemia—acute myeloid leukemia (AML) Accessed Feb 1 2019.
  7. 7.
    Im AP, Sehgal AR, Carroll MP, et al. DNMT3A and IDH mutations in acute myeloid leukemia and other myeloid malignancies: associations with prognosis and potential treatment strategies. Leukemia. 2014;28(9):1774–83.CrossRefGoogle Scholar
  8. 8.
    Mondesir J, Willekens C, Touat M, et al. IDH1 and IDH2 mutations as novel therapeutic targets: current perspectives. J Blood Med. 2016;7:171–80.CrossRefGoogle Scholar
  9. 9.
    Ward PS, Patel J, Wise DR, et al. The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting α-ketoglutarate to 2-hydroxyglutarate. Cancer Cell. 2010;17(3):225–34.CrossRefGoogle Scholar
  10. 10.
    Dang L, White DW, Gross S, et al. Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature. 2009;462(7274):739–44.CrossRefGoogle Scholar
  11. 11.
    Lu C, Ward PS, Kapoor GS, et al. IDH mutation impairs histone demethylation and results in a block to cell differentiation. Nature. 2012;483(7390):474–8.CrossRefGoogle Scholar
  12. 12.
    Krell D, Mulholland P, Frampton AE, et al. IDH mutations in tumorigenesis and their potential role as novel therapeutic targets. Future Oncol. 2013;9(12):1923–35.CrossRefGoogle Scholar
  13. 13.
    Figueroa ME, Abdel-Wahab O, Lu C, et al. Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation. Cancer Cell. 2010;18(6):553–67.CrossRefGoogle Scholar
  14. 14.
    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):732–6.CrossRefGoogle Scholar
  15. 15.
    Dohner H, Estey EH, Amadori S, et al. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood. 2010;115(3):453–74.CrossRefGoogle Scholar
  16. 16.
    Bullinger L, Dohner K, Dohner H. Genomics of acute myeloid leukemia diagnosis and pathways. J Clin Oncol. 2017;35(9):934–46.CrossRefGoogle Scholar
  17. 17.
    Schwaederle M, Zhao M, Lee JJ, et al. Impact of precision medicine in diverse cancers: a meta-analysis of phase II clinical trials. J Clin Oncol. 2015;33(32):3817–25.CrossRefGoogle Scholar
  18. 18.
    Tibsovo® (ivosidenib) tablets, for oral use: US prescribing information. Cambridge: Agios Pharmaceuticals Inc.; 2018.Google Scholar
  19. 19.
    Popovici-Muller J, Lemieux RM, Artin E, et al. Discovery of AG-120 (ivosidenib): a first-in-class mutant IDH1 inhibitor for the treatment of IDH1 mutant cancers. ACS Med Chem Lett. 2018;9(4):300–5.CrossRefGoogle Scholar
  20. 20.
    IDH program. Cambridge: Agios Pharmaceuticals Inc.; 2018. Accessed 1 Feb 2019.
  21. 21.
    DiNardo CD, Stein EM, de Botton S, et al. Durable remissions with ivosidenib in IDH1-mutated relapsed or refractory AML. N Engl J Med. 2018;378(25):2386–98.CrossRefGoogle Scholar
  22. 22.
    Cheson BD, Bennett JM, Kopecky KJ, et al. Revised recommendations of the International Working Group for diagnosis, standardization of response criteria, treatment outcomes, and reporting standards for therapeutic trials in acute myeloid leukemia. J Clin Oncol. 2003;21(24):4642–9.CrossRefGoogle Scholar
  23. 23.
    Birendra KC, DiNardo CD. Evidence for clinical differentiation and differentiation syndrome in patients with acute myeloid leukemia and IDH1 mutations treated with the targeted mutant IDH1 inhibitor, AG-120. Clin Lymphoma Myeloma Leuk. 2016;16(8):460–5.CrossRefGoogle Scholar
  24. 24.
    Norsworthy JK, Mulkey F, Ward AF, et al. Incidence of differentiation syndrome with ivosidenib (IVO) and enasidenib (ENA) for treatment of patients with relapsed or refractory (R/R) isocitrate dehydrogenase (IDH)1- or IDH2-mutated acute myeloid leukemia (AML): a systematic analysis by the U.S. Food and Drug Administration (FDA) [abstract no. 288]. In: 60th American Society of Hematology Annual Meeting. 2018.Google Scholar
  25. 25.
    Montesinos P, Bergua JM, Vellenga E, et al. Differentiation syndrome in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline chemotherapy: characteristics, outcome, and prognostic factors. Blood. 2009;113(4):775–83.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.SpringerAucklandNew Zealand

Personalised recommendations