Durable Remissions with Ivosidenib in IDH1-Mutated Relapsed or Refractory AML
Courtney D. DiNardo,Eytan M. Stein,S. de Botton,Gail J. Roboz,Jessica K. Altman,Alice S. Mims,Ronan T. Swords,Robert H. Collins,Gabriel N. Mannis,Daniel A. Pollyea,William B. Donnellan,Amir T. Fathi,A. Pigneux,Harry P. Erba,Gabrielle T. Prince,Anthony S. Stein,Geoffrey L. Uy,James M. Foran,Elie Traer,Robert K. Stuart,Martha Arellano,James L. Slack,Mikkael A. Sekeres,Christophe Willekens,Sung Choe,Hongfang Wang,Vickie Zhang,Katharine E. Yen,Stephanie M. Kapsalis,Hua Yang,David Dai,Bin Fan,Meredith Goldwasser,Hua Liu,Samuel V. Agresta,Bin Wu,Eyal C. Attar,Martin S. Tallman,Richard Stone,Hagop M. Kantarjian +39 more
TLDR
In patients with advanced IDH1‐mutated relapsed or refractory AML, ivosidenib at a dose of 500 mg daily was associated with a low frequency of grade 3 or higher treatment‐related adverse events and with transfusion independence, durable remissions, and molecular remissions in some patients with complete remission.Abstract:
Background Mutations in the gene encoding isocitrate dehydrogenase 1 (IDH1) occur in 6 to 10% of patients with acute myeloid leukemia (AML). Ivosidenib (AG-120) is an oral, targeted, small-molecule inhibitor of mutant IDH1. Methods We conducted a phase 1 dose-escalation and dose-expansion study of ivosidenib monotherapy in IDH1-mutated AML. Safety and efficacy were assessed in all treated patients. The primary efficacy population included patients with relapsed or refractory AML receiving 500 mg of ivosidenib daily with at least 6 months of follow-up. Results Overall, 258 patients received ivosidenib and had safety outcomes assessed. Among patients with relapsed or refractory AML (179 patients), treatment-related adverse events of grade 3 or higher that occurred in at least 3 patients were prolongation of the QT interval (in 7.8% of the patients), the IDH differentiation syndrome (in 3.9%), anemia (in 2.2%), thrombocytopenia or a decrease in the platelet count (in 3.4%), and leukocytosis (in 1.7%...read more
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Acute myeloid leukemia, version 3.2017: Clinical practice guidelines in oncology
Margaret R. O'Donnell,Martin S. Tallman,Camille N. Abboud,Jessica K. Altman,Frederick R. Appelbaum,Daniel A. Arber,Vijaya Raj Bhatt,Dale L. Bixby,William Blum,Steven Coutre,Marcos de Lima,Amir T. Fathi,Melanie Fiorella,James M. Foran,Steven D. Gore,Aric C. Hall,Patricia Kropf,Jeffrey E. Lancet,Lori J. Maness,Guido Marcucci,Michael Gary Martin,Joseph O. Moore,Rebecca L. Olin,Deniz Peker,Daniel A. Pollyea,Keith W. Pratz,Farhad Ravandi,Paul J. Shami,Richard Stone,Stephen A. Strickland,Eunice S. Wang,Matthew J. Wieduwilt,Kristina M. Gregory,Ndiya Ogba +33 more
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Ivosidenib in IDH1-mutant, chemotherapy-refractory cholangiocarcinoma (ClarIDHy): a multicentre, randomised, double-blind, placebo-controlled, phase 3 study
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