Ivosidenib to treat adult patients with relapsed or refractory acute myeloid leukemia.

• Pasquier, F. ^[2] ; Lecuit, M. ^[2] ; Broutin, S. ^[6] ; Saada, V. ^[3] ; Jeanson, A. ^[4] ; Penard-Lacronique, V. ^[1] ; de Botton, S. ^{[2] [4] [1] [5]}
  1. [1] Gustave Roussy Cancer Campus

     Gustave Roussy Cancer Campus

     Arrondissement de L'Haÿ-les-Roses, Francia

     
  2. [2] Department of Clinical Research, Gustave Roussy Cancer Center, Villejuif, France
  3. [3] Department of Biopathology, Gustave Roussy Cancer Center, Villejuif, France
  4. [4] Department of Therapeutic Innovations and Early Trials (DITEP), Gustave Roussy Cancer Center, Villejuif, France
  5. [5] Paris-Sud University, Kremlin-Bicêtre, France
  6. [6] Department of Pharmacology, Gustave Roussy Cancer Center, Villejuif, France

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• Localización: Medicamentos de actualidad = Drugs of today, ISSN 1699-3993, Vol. 56, Nº. 1, 2020, págs. 21-35
• Idioma: inglés
• Texto completo no disponible (Saber más ...)
• Resumen

  • Isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) are key metabolic enzymes that convert isocitrate to alpha-ketoglutarate (alphaKG). Somatic point mutations in IDH1/2 that are found in rare distinct subsets of cancers confer a gain of function in cancer cells which results in the accumulation and secretion in vast excess of the oncometabolite D-2-hydroxyglutarate (D-2HG). Overproduction of D-2HG interferes with cellular metabolism and epigenetic regulation, contributing to oncogenesis. High levels of D-2HG inhibit alphaKG-dependent dioxygenases including histone, DNA and RNA demethylases, resulting in histone, DNA and RNA hypermethylation and cell differentiation blockade. In addition, D-2HG is a biomarker suitable for the detection of IDH1/2 mutations at diagnosis, and is also predictive of clinical response. The U.S. Food and Drug Administration (FDA) approved ivosidenib, a mutant-IDH1 enzyme inhibitor, for patients with relapsed or refractory IDH1-mutated acute myeloid leukemia (AML) in 2018, and also as front-line therapy for newly diagnosed elderly patients 75 years or older or who are ineligible to receive intensive chemotherapy in 2019. Ivosidenib represents a novel drug class for targeted therapy in AML.