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Blood. 2019 Dec 16. pii: blood.2019002140. doi: 10.1182/blood.2019002140. [Epub ahead of print]

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

Author information

1
Weill Medical College of Cornell University, New York, New York, United States.
2
UT MD Anderson Cancer Center, Houston, Texas, United States.
3
Memorial Sloan Kettering Cancer Center, New York, New York, United States.
4
Institut Gustave Roussy, Villejuif, France.
5
The Ohio State University, Columbus, Ohio, United States.
6
Johns Hopkins University, Baltimore, Maryland, United States.
7
Northwestern University, Chicago, Illinois, United States.
8
Winship Cancer Institute of Emory University, Atlanta, Georgia, United States.
9
Sarah Cannon Research Institute, Nashville, Tennessee, United States.
10
University of Alabama at Birmingham, Birmingham, AL, United States.
11
UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, United States.
12
University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States.
13
City of Hope National Medical Center, Duarte, California, United States.
14
Washington University School of Medicine, Saint Louis, Missouri, United States.
15
University of Miami Miller School of Medicine, Miami, Florida, United States.
16
Massachusetts General Hospital, Boston, Massachusetts, United States.
17
University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States.
18
Memorial Sloan-Kettering Cancer Center, New York, New York, United States.
19
Agios Pharmaceuticals, Inc., Cambridge, Massachusetts, United States.
20
Auron Therapeutics, Wellesley, Massachusetts, United States.
21
Foghorn Pharmaceuticals, Inc., Cambridge, Massachusetts, United States.
22
Agios, Cambridge, Massachusetts, United States.
23
Aprea, Boston, Massachusetts, United States.
24
Dana-Farber Cancer Institute, Boston, Massachusetts, United States.

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 (mIDH1) enzyme. From a phase 1 study of 258 patients with IDH1-mutant advanced hematologic malignancies, we report results for 34 patients with newly diagnosed acute myeloid leukemia (AML) ineligible for standard therapy who received ivosidenib 500 mg once daily. Median age was 76.5 years, 26 (76%) patients had secondary AML and 16 (47%) had received {greater than or equal to}1 hypomethylating agent for an antecedent hematologic disorder. The most common all-grade adverse events were diarrhea (n=18; 53%), fatigue (n=16; 47%), nausea (n=13; 38%), and decreased appetite (n=12; 35%). Differentiation syndrome was reported in 6 (18%) patients (grade {greater than or equal to}3 in 3 [9%]) and did not require treatment discontinuation. Complete remission (CR) + CR with partial hematologic recovery (CRh) rate was 42.4% (95% confidence interval [CI], 25.5-60.8%); CR rate was 30.3% (95% CI, 15.6-48.7%). Median durations of CR+CRh 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), median overall survival was 12.6 months (95% CI, 4.5-25.7). Of 21 (63.6%) patients who were transfusion dependent at baseline, 9 (42.9%) became transfusion independent. IDH1 mutation clearance was seen in 9/14 patients achieving CR+CRh (5/10 CR, 4/4 CRh). Ivosidenib monotherapy was well tolerated and induced durable remissions and transfusion independence in patients with newly diagnosed AML. (Trial registered at www.clinicaltrials.gov #NCT02074839.).

PMID:
31841594
DOI:
10.1182/blood.2019002140

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