IDH1-mutated relapsed or refractory AML: current challenges and future prospects
Juan Eduardo Megías-Vericat,1 Octavio Ballesta-López,1 Eva Barragán,2,3 Pau Montesinos2,31Servicio de Farmacia, Área del Medicamento, Hospital Universitari i Politècnic La Fe, Valencia, Spain; 2Servicio de Hematología y Hemoterapia, H...
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| Autores principales: | , , , |
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| Formato: | article |
| Lenguaje: | EN |
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Dove Medical Press
2019
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/644517ea4c7d4750a7e0382dca92bc5f |
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| Sumario: | Juan Eduardo Megías-Vericat,1 Octavio Ballesta-López,1 Eva Barragán,2,3 Pau Montesinos2,31Servicio de Farmacia, Área del Medicamento, Hospital Universitari i Politècnic La Fe, Valencia, Spain; 2Servicio de Hematología y Hemoterapia, Hospital Universitari i Politècnic La Fe, Valencia, Spain; 3CIBERONC, Instituto Carlos III, Madrid, SpainAbstract: The prognosis of patients with relapsed or refractory acute myeloid leukemia (R/R AML) is discouraging with salvage standard approaches. Mutations of isocitrate dehydrogenase 1 (IDH1mut,), present in 7–14% of AML patients, have been discovered recently, opening the door to targeted agents aiming to improve the outcomes in this setting. Several oral selective IDH1mut, inhibitors are under investigation, ivosidenib being the first approved for R/R AML. We performed a systematic review to analyze the clinical outcomes and safety reported with IDH1mut, inhibitors and other agents in adult patients with IDH1mut, R/R AML. Ivosidenib in monotherapy achieved complete remission (CR) of 24%, overall response of 42%, and median overall survival of 9 months in R/R AML, and promising outcomes were reported with IDH305 and FT-2102. IDH1mut, inhibitors were generally well tolerated, but some therapy-related toxicities should be monitored, including IDH-differentiation syndrome, prolongation of the QT interval, and leukocytosis, all manageable and reversible. Also, venetoclax, CB-839, PARP inhibitors, and IDH1 peptide vaccine are being studied in IDH1mut, AML. The results of the ongoing and upcoming clinical trials will bring new evidence to establish the role of IDH1mut, inhibitors in therapeutic strategies of AML.Keywords: isocitrate dehydrogenase 1, acute myeloid leukemia, relapsed/refractory, ivosidenib, FT-2102, venetoclax |
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