Ivosidenib induces deep durable remissions in patients with newly diagnosed IDH1-mutant acute myeloid leukemia

Gail J. Roboz*, Courtney D. DiNardo, Eytan M. Stein, Stéphane de Botton, Alice S. Mims, Gabrielle T. Prince, Jessica K. Altman, Martha L. Arellano, Will Donnellan, Harry P. Erba, Gabriel N. Mannis, Daniel A. Pollyea, Anthony S. Stein, Geoffrey L. Uy, Justin M. Watts, Amir T. Fathi, Hagop M. Kantarjian, Martin S. Tallman, Sung Choe, David DaiBin Fan, Hongfang Wang, Vickie Zhang, Katharine E. Yen, Stephanie M. Kapsalis, Denice Hickman, Hua Liu, Samuel V. Agresta, Bin Wu, Eyal C. Attar, Richard M. Stone

*Corresponding author for this work

Research output: Contribution to journalReview article

14 Scopus citations

Abstract

Ivosidenib (AG-120) is an oral, targeted agent that suppresses production of the oncometabolite 2-hydroxyglutarate via inhibition of the mutant isocitrate dehydrogenase 1 (IDH1; mIDH1) enzyme. From a phase 1 study of 258 patients with IDH1-mutant hematologic malignancies, we report results for 34 patients with newly diagnosed acute myeloid leukemia (AML) ineligible for standard therapy who received 500 mg ivosidenib daily. Median age was 76.5 years, 26 patients (76%) had secondary AML, and 16 (47%) had received ‡1 hypomethylating agent for an antecedent hematologic disorder. The most common all-grade adverse events were diarrhea (n 5 18; 53%), fatigue (n 5 16; 47%), nausea (n 5 13; 38%), and decreased appetite (n 5 12; 35%). Differentiation syndrome was reported in 6 patients (18%) (grade ‡3 in 3 [9%]) and did not require treatment discontinuation. Complete remission (CR) plus CR with partial hematologic recovery (CRh) rate was 42.4% (95% confidence interval [CI], 25.5% to 60.8%); CR 30.3% (95% CI, 15.6% to 48.7%). Median durations of CR1CRh and CR were not reached, with 95% CI lower bounds of 4.6 and 4.2 months, respectively; 61.5% and 77.8% of patients remained in remission at 1 year. With median follow-up of 23.5 months (range, 0.6-40.9 months), median overall survival was 12.6 months (95% CI, 4.5-25.7). Of 21 transfusion-dependent patients (63.6%) at baseline, 9 (42.9%) became transfusion independent. IDH1 mutation clearance was seen in 9/14 patients achieving CR1CRh (5/10 CR; 4/4 CRh). Ivosidenib monotherapy was well-tolerated and induced durable remissions and transfusion independence in patients with newly diagnosed AML. This trial was registered at www.clinicaltrials.gov as #NCT02074839. (Blood. 2020;135(7):463-471)

Original languageEnglish (US)
Pages (from-to)463-471
Number of pages9
JournalBlood
Volume135
Issue number7
DOIs
StatePublished - Feb 13 2020

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Roboz, G. J., DiNardo, C. D., Stein, E. M., de Botton, S., Mims, A. S., Prince, G. T., Altman, J. K., Arellano, M. L., Donnellan, W., Erba, H. P., Mannis, G. N., Pollyea, D. A., Stein, A. S., Uy, G. L., Watts, J. M., Fathi, A. T., Kantarjian, H. M., Tallman, M. S., Choe, S., ... Stone, R. M. (2020). Ivosidenib induces deep durable remissions in patients with newly diagnosed IDH1-mutant acute myeloid leukemia. Blood, 135(7), 463-471. https://doi.org/10.1182/blood.2019002140