Acute myeloid leukemia, IDH-mutated

Section editor
	Martin W. Schoen, MD, MPH Saint Louis University St. Louis, MO mwschoen

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

8 regimens on this page 8 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

• Alteration: IDH1 R132 gene variant

Chemotherapy

• Ivosidenib (Tibsovo) 500 mg PO once per day

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 [1] NCT02074839

IDH1 relapsed or refractory, salvage therapy

Ivosidenib monotherapy

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Regimen

FDA-recommended dose

Study	Evidence	Efficacy
DiNardo et al. 2018 (AG120-C-001)	Phase I/II (RT)	ORR: 42%

Biomarker eligibility criteria

• Alteration: IDH1 R132 gene variant

Chemotherapy

• Ivosidenib (Tibsovo) 500 mg PO once per day

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

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Study	Evidence
AG120-C-001	Phase I/II

Biomarker eligibility criteria

• Alteration: IDH2 gene variant

Chemotherapy

• Enasidenib (Idhifa) 100 mg PO once per day

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. Pubmed NCT01915498

IDH2 Relapsed or refractory, salvage therapy

Enasidenib monotherapy

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Regimen

FDA-recommended dose

Study	Evidence	Efficacy
Stein et al. 2017 (AG-221-C-001)	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

• Enasidenib (Idhifa) 100 mg PO once per day

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