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


Authors: 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.; Dai, D.; Fan, B.; Wang, H.; Zhang, V.; Yen, K. E.; Kapsalis, S. M.; Hickman, D.; Liu, H.; Agresta, S. V.; Wu, B.; Attar, E. C.; Stone, R. M.
Article Title: Ivosidenib induces deep durable remissions in patients with newly diagnosed IDH1-mutant acute myeloid leukemia
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) © 2020 by The American Society of Hematology
Journal Title: Blood
Volume: 135
Issue: 7
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 2020-02-13
Start Page: 463
End Page: 471
Language: English
DOI: 10.1182/blood.2019002140
PUBMED: 31841594
PROVIDER: scopus
PMCID: PMC7019193
DOI/URL:
Notes: Review -- Export Date: 2 March 2020 -- Source: Scopus
Altmetric
Citation Impact
MSK Authors
  1. Eytan Moshe Stein
    144 Stein
  2. Martin Stuart Tallman
    486 Tallman