Acute myeloid leukemia, IDH-mutated

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Martin W. Schoen, MD, MPH
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Note: these are regimens tested in biomarker-specific populations for patients with IDH-mutated AML, please see the main AML page for other regimens.

3 regimens on this page
3 variants on this page


IDH1 first-line therapy, older or 'unfit' patients

Ivosidenib monotherapy

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Regimen

FDA-recommended dose
Study Evidence
AG120-C-001 Phase I/II

Biomarker eligibility criteria

  • Gene: IDH1
  • Alteration: R132

Chemotherapy

Continued indefinitely

References

  1. AG120-C-001: Roboz GJ, DiNardo CD, Stein EM, de Botton S, Mims AS, Prince GT, Altman JK, Arellano ML, Donnellan WB, Erba HP, Mannis GN, Pollyea DA, Stein AS, Uy GL, Watts JM, Fathi AT, Kantarjian HM, Tallman MS, Choe S, Dai D, Fan B, Wang H, Zhang V, Yen KE, Kapsalis SM, Hickman D, Liu H, Agresta SV, Wu B, Attar EC, Stone RM. Ivosidenib induces deep durable remissions in patients with newly diagnosed IDH1-mutant acute myeloid leukemia. Blood. 2019 Dec 16. [Epub ahead of print] link to original article NCT02074839

IDH1 relapsed or refractory, salvage therapy

Ivosidenib monotherapy

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Regimen

FDA-recommended dose
Study Years of enrollment Evidence Efficacy
DiNardo et al. 2018 (AG120-C-001) 2014-2017 Phase I/II (RT) ORR: 42%

Biomarker eligibility criteria

  • Alteration: IDH1 R132 gene variant

Chemotherapy

Continued indefinitely

References

  1. AG120-C-001: DiNardo CD, Stein EM, de Botton S, Roboz GJ, Altman JK, Mims AS, Swords R, Collins RH, Mannis GN, Pollyea DA, Donnellan W, Fathi AT, Pigneux A, Erba HP, Prince GT, Stein AS, Uy GL, Foran JM, Traer E, Stuart RK, Arellano ML, Slack JL, Sekeres MA, Willekens C, Choe S, Wang H, Zhang V, Yen KE, Kapsalis SM, Yang H, Dai D, Fan B, Goldwasser M, Liu H, Agresta S, Wu B, Attar EC, Tallman MS, Stone RM, Kantarjian HM. Durable remissions with ivosidenib in IDH1-mutated relapsed or refractory AML. N Engl J Med. 2018 Jun 21;378(25):2386-2398. Epub 2018 Jun 2. link to original article contains protocol PubMed

IDH2 first-line therapy, older or 'unfit' patients

Enasidenib monotherapy

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Regimen

Study Evidence
Pollyea et al. 2019 AG120-C-001 Phase I/II

Biomarker eligibility criteria

  • Alteration: IDH2 gene variant

Chemotherapy

28-day cycles

References

  1. AG-221-C-001: Pollyea DA, Tallman MS, de Botton S, Kantarjian HM, Collins R, Stein AS, Frattini MG, Xu Q, Tosolini A, See WL, MacBeth KJ, Agresta SV, Attar EC, DiNardo CD, Stein EM. Enasidenib, an inhibitor of mutant IDH2 proteins, induces durable remissions in older patients with newly diagnosed acute myeloid leukemia. Leukemia. 2019 Nov;33(11):2575-2584. Epub 2019 Apr 9. link to original article Pubmed

IDH2 Relapsed or refractory, salvage therapy

Enasidenib monotherapy

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Regimen

FDA-recommended dose
Study Years of enrollment Evidence Efficacy
Stein et al. 2017 (AG-221-C-001) 2013-2016 Phase I/II (RT) ORR: 40%

This is the dose used in the phase II expansion cohort; enrolled patients were required to have IDH2-mutated advanced myeloid malignancies.

Biomarker eligibility criteria

  • Alteration: IDH2 gene variant

Chemotherapy

28-day cycles

References

  1. AG-221-C-001: Stein EM, DiNardo CD, Pollyea DA, Fathi AT, Roboz GJ, Altman JK, Stone RM, DeAngelo DJ, Levine RL, Flinn IW, Kantarjian HM, Collins R, Patel MR, Frankel AE, Stein A, Sekeres MA, Swords RT, Medeiros BC, Willekens C, Vyas P, Tosolini A, Xu Q, Knight RD, Yen KE, Agresta S, de Botton S, Tallman MS. Enasidenib in mutant IDH2 relapsed or refractory acute myeloid leukemia. Blood. 2017 Aug 10;130(6):722-731. Epub 2017 Jun 6. link to original article contains verified protocol link to PMC article PubMed