Details

Autor(en) / Beteiligte

• Norsworthy, Kelly J
• Luo, Lola
• Hsu, Vicky
• Gudi, Ramadevi
• Dorff, Sarah E
• Przepiorka, Donna
• Deisseroth, Albert
• Shen, Yuan-Li
• Sheth, Christopher M
• Charlab, Rosane
• Williams, Gene M
• Goldberg, Kirsten B
• Farrell, Ann T
• Pazdur, Richard

Titel

FDA Approval Summary: Ivosidenib for Relapsed or Refractory Acute Myeloid Leukemia with an Isocitrate Dehydrogenase-1 Mutation

Ist Teil von

• Clinical cancer research, 2019-06, Vol.25 (11), p.3205-3209

Ort / Verlag

United States

Erscheinungsjahr

2019

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• The FDA approved ivosidenib (Tibsovo; Agios), a small-molecule inhibitor of isocitrate dehydrogenase (IDH)1 on July 20, 2018, for treatment of adults with relapsed or refractory acute myeloid leukemia (R/R AML) with susceptible IDH1 mutation as detected by an FDA-approved test. The efficacy of ivosidenib was established on the basis of complete remission (CR) + CR with partial hematologic recovery (CRh) rate, duration of CR + CRh, and conversion from transfusion dependence (TD) to transfusion independence (TI) in Study AG120-C-001, a single-arm trial. With median follow-up of 8.3 months for 174 adults with IDH1-mutated R/R AML treated with 500 mg ivosidenib daily, the CR + CRh rate was 33% [95% confidence interval (CI), 26-40], median duration of response was 8.2 (95% CI, 5.6-12) months, and conversion from TD to TI occurred in 37% of patients. These endpoints reflect short-term benefit in patients with an unmet medical need; long-term efficacy outcomes were not assessed. Serious adverse reactions (AR) in ≥5% of patients were differentiation syndrome (10%), leukocytosis (10%), and QT interval prolongation (7%). Common (≥20%) ARs of any grade were fatigue, leukocytosis, arthralgia, diarrhea, dyspnea, edema, nausea, mucositis, QT interval prolongation, rash, pyrexia, cough, and constipation. Assessment of long-term safety of ivosidenib is a condition of this approval.