Abstract
FLT3 mutations, characterized by an internal-tandem duplication or missense mutations in the tyrosine kinase domain, are observed in a third of patients with newly diagnosed acute myeloid leukemia. FLT3-ITD mutations are associated with high relapse rates and short overall survival with conventional chemotherapy. Several tyrosine kinase inhibitors targeting FLT3 have been developed in an effort to improve survival and therapeutic options. This review focuses on quizartinib, a second-generation FLT3 inhibitor that has demonstrated efficacy and safety as a single agent and in combination with chemotherapy. We discuss its clinical development as well as its place in the treatment of FLT3-mutated acute myeloid leukemia among the other FLT3 inhibtors currently available and its mechanisms of resistance.
Keywords:
FLT3 mutation; FLT3-ITD AML; acute myeloid leukemia; quizartinib.
MeSH terms
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Animals
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Antineoplastic Combined Chemotherapy Protocols / pharmacology*
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use
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Benzothiazoles / pharmacology*
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Benzothiazoles / therapeutic use
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Disease Models, Animal
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Disease-Free Survival
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Dose-Response Relationship, Drug
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Drug Evaluation, Preclinical
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Drug Resistance, Neoplasm / genetics
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Gene Duplication
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Humans
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Leukemia, Myeloid, Acute / drug therapy*
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Leukemia, Myeloid, Acute / genetics
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Leukemia, Myeloid, Acute / mortality
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Neoplasm Recurrence, Local / drug therapy*
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Neoplasm Recurrence, Local / epidemiology
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Neoplasm Recurrence, Local / genetics
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Phenylurea Compounds / pharmacology*
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Phenylurea Compounds / therapeutic use
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Protein Kinase Inhibitors / pharmacology*
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Protein Kinase Inhibitors / therapeutic use
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Randomized Controlled Trials as Topic
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fms-Like Tyrosine Kinase 3 / genetics*
Substances
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Benzothiazoles
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Phenylurea Compounds
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Protein Kinase Inhibitors
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quizartinib
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FLT3 protein, human
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fms-Like Tyrosine Kinase 3