Enasidenib in mutant IDH2 relapsed or refractory acute myeloid leukemia

• Published in: Blood Vol. 130; no. 6; pp. 722 - 731
• Main Authors: Stein, Eytan M., DiNardo, Courtney D., Pollyea, Daniel A., Fathi, Amir T., Roboz, Gail J., Altman, Jessica K., Stone, Richard M., DeAngelo, Daniel J., Levine, Ross L., Flinn, Ian W., Kantarjian, Hagop M., Collins, Robert, Patel, Manish R., Frankel, Arthur E., Stein, Anthony, Sekeres, Mikkael A., Swords, Ronan T., Medeiros, Bruno C., Willekens, Christophe, Vyas, Paresh, Tosolini, Alessandra, Xu, Qiang, Knight, Robert D., Yen, Katharine E., Agresta, Sam, de Botton, Stephane, Tallman, Martin S.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 10.08.2017; American Society of Hematology
• Subjects: Adult; Aged; Aged, 80 and over; Aminopyridines - adverse effects; Aminopyridines - pharmacokinetics; Aminopyridines - therapeutic use; Antineoplastic Agents - adverse effects; Antineoplastic Agents - pharmacokinetics; Antineoplastic Agents - therapeutic use; Bone Marrow - drug effects; Bone Marrow - metabolism; Bone Marrow - pathology; Clinical Trials and Observations; Enzyme Inhibitors - adverse effects; Enzyme Inhibitors - pharmacokinetics; Enzyme Inhibitors - therapeutic use; Female; Humans; Isocitrate Dehydrogenase - antagonists & inhibitors; Isocitrate Dehydrogenase - genetics; Leukemia, Myeloid, Acute - drug therapy; Leukemia, Myeloid, Acute - genetics; Leukemia, Myeloid, Acute - pathology; Male; Maximum Tolerated Dose; Middle Aged; Mutation; Neoplasm Recurrence, Local - drug therapy; Neoplasm Recurrence, Local - genetics; Neoplasm Recurrence, Local - pathology; Triazines - adverse effects; Triazines - pharmacokinetics; Triazines - therapeutic use; Young Adult

Recurrent mutations in isocitrate dehydrogenase 2 (IDH2) occur in ∼12% of patients with acute myeloid leukemia (AML). Mutated IDH2 proteins neomorphically synthesize 2-hydroxyglutarate resulting in DNA and histone hypermethylation, which leads to blocked cellular differentiation. Enasidenib (AG-221/...