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Durable Remissions with Ivosidenib in IDH1-Mutated Relapsed or Refractory AML
Courtney D DiNardo1, Eytan M Stein1, Stéphane de Botton1
1From the University of Texas M.D. Anderson Cancer Center, Houston (C.D.D., H.M.K.); Memorial Sloan Kettering Cancer Center (E.M.S., M.S.T.) and Weill Cornell Medical College (G.J.R.), New York; Institut Gustave Roussy, Villejuif (S.B., C.W.), and Centre Hospitalier Universitaire Bordeaux, Bordeaux (A.P.) - both in France; Northwestern University, Chicago (J.K.A.); Ohio State University Wexner Medical Center, Columbus (A.S.M.); Sylvester Comprehensive Cancer Center, University of Miami, Miami (R.S.); University of Texas Southwestern Medical Center, Dallas (R.H.C.); University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco (G.N.M.), and City of Hope Medical Center, Duarte (A.S.S.) - both in California; University of Colorado School of Medicine, Aurora (D.A.P.); Sarah Cannon Research Institute, Nashville (W.D.); Massachusetts General Hospital Cancer Center (A.T.F.) and Dana-Farber Cancer Institute (R.M.S.), Boston, and Agios Pharmaceuticals, Cambridge (S.C., H.W., V.Z., K.E.Y., S.M.K., H.Y., D.D., B.F., M.G., H.L., S.A., B.W., E.C.A.) - all in Massachusetts; University of Alabama at Birmingham, Birmingham (H.P.E.); Johns Hopkins University, Baltimore (G.T.P.); Washington University School of Medicine, St. Louis (G.L.U.); Mayo Clinic, Jacksonville, FL (J.M.F.); Oregon Health and Science University Knight Cancer Institute, Portland (E.T.); Hollings Cancer Center, Medical University of South Carolina, Charleston (R.K.S.); Winship Cancer Institute of Emory University, Atlanta (M.L.A.); Mayo Clinic, Phoenix, AZ (J.L.S.); and Cleveland Clinic, Cleveland (M.A.S.).
Ivosidenib is an effective targeted therapy for acute myeloid leukemia (AML) with IDH1 mutations. This treatment showed durable remissions and molecular responses in relapsed or refractory AML patients.
Area of Science:
- Oncology
- Hematology
- Pharmacology
Background:
- Isocitrate dehydrogenase 1 (IDH1) mutations are present in 6-10% of acute myeloid leukemia (AML) patients.
- Ivosidenib (AG-120) is an oral, targeted small-molecule inhibitor specifically designed for mutant IDH1.
Purpose of the Study:
- To evaluate the safety and efficacy of ivosidenib monotherapy in patients with IDH1-mutated AML.
- To assess outcomes in patients with relapsed or refractory AML receiving a specific dose of ivosidenib.
Main Methods:
- A Phase 1 dose-escalation and dose-expansion study was conducted.
- Safety and efficacy were assessed in 258 patients.
- The primary efficacy population comprised 125 patients with relapsed/refractory AML receiving 500 mg of ivosidenib daily, with at least 6 months of follow-up.
Main Results:
- Complete remission (CR) or CR with partial hematologic recovery was achieved in 30.4% of patients.
- The overall response rate (ORR) was 41.6%, with a median response duration of 6.5-9.3 months.
- Transfusion independence was achieved in 35% of patients, and some achieved molecular remission.
Conclusions:
- Ivosidenib (500 mg daily) demonstrates a favorable safety profile with a low incidence of severe adverse events in advanced IDH1-mutated relapsed/refractory AML.
- The treatment is associated with transfusion independence, durable remissions, and molecular remissions in a subset of patients.
- Ivosidenib represents a promising targeted therapy for IDH1-mutated AML.
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