FDA Approval Summary: Olutasidenib for Adult Patients with Relapsed or Refractory Acute Myeloid Leukemia with an <i>Isocitrate Dehydrogenase 1</i> Mutation
Ashley Woods, Kelly J. Norsworthy, Moran Choe, Brenda J. Gehrke, Haiyan Chen, Jonathon Vallejo, Lili Pan, Xiling Jiang, Hongshan Li, Jeffrey Kraft, Jiang Liu, Rosane Charlab, Ólanrewaju O. Okusanya, Brian Booth, Richard Pazdur, Marc R. Theoret, R. Angelo de Claro
Abstract
On December 1, 2022, the FDA approved the new molecular entity olutasidenib (Rezlidhia, Rigel Pharmaceuticals), a small-molecule inhibitor of isocitrate dehydrogenase 1, for the treatment of adult patients with relapsed or refractory acute myeloid leukemia with a susceptible isocitrate dehydrogenase 1 mutation as detected by an FDA-approved test. The efficacy of olutasidenib was established based on complete remission (CR) + CR with partial hematologic recovery (CRh) rate, duration of CR + CRh, and conversion of transfusion dependence to transfusion independence in Study 2102-HEM-101. In the pivotal trial, 147 adult patients treated with 150 mg twice daily of olutasidenib were evaluable for efficacy. With a median follow-up of 10.2 months, the CR/CRh rate was 35% (95% confidence interval, 27%-43%), with a median duration of response of 25.9 months [95% confidence interval, 13.5-not reached]. Of the 86 patients who were transfusion dependent at baseline, 29 became transfusion independent (34%). The most common (≥20%) adverse reactions were nausea, fatigue, arthralgia, leukocytosis, dyspnea, pyrexia, rash, mucositis, diarrhea, and transaminitis. An assessment of long-term safety of olutasidenib is a condition of this approval.