FLT3 inhibitors in acute myeloid leukemia: ten frequently asked questions
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Springer Nature
Abstract
The FMS-like tyrosine kinase 3 (FLT3) gene is mutated in approximately one third of patients with acute myeloid leukemia (AML), either by internal tandem duplications (FLT3-ITD), or by a point mutation mainly involving the tyrosine kinase domain (FLT3-TKD). Patients with FLT3-ITD have a high risk of relapse and low cure rates. Several FLT3 tyrosine kinase inhibitors have been developed in the last few years with variable kinase inhibitory properties, pharmacokinetics, and toxicity profiles. FLT3 inhibitors are divided into first generation multi-kinase inhibitors (such as sorafenib, lestaurtinib, midostaurin) and next generation inhibitors (such as quizartinib, crenolanib, gilteritinib) based on their potency and specificity of FLT3 inhibition. These diverse FLT3 inhibitors have been evaluated in myriad clinical trials as monotherapy or in combination with conventional chemotherapy or hypomethylating agents and in various settings, including front-line, relapsed or refractory disease, and maintenance therapy after consolidation chemotherapy or allogeneic stem cell transplantation. In this practical question-and-answer-based review, the main issues faced by the leukemia specialists on the use of FLT3 inhibitors in AML are addressed. © 2020, The Author(s), under exclusive licence to Springer Nature Limited.
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Aniline compounds, Antineoplastic agents, Benzimidazoles, Benzothiazoles, Carbazoles, Dna methylation, Enzyme inhibitors, Fms-like tyrosine kinase 3, Humans, Leukemia, myeloid, acute, Mutation, Neoplasm recurrence, local, Phenylurea compounds, Piperidines, Prognosis, Pyrazines, Randomized controlled trials as topic, Sorafenib, Staurosporine, Treatment outcome, Angiogenesis inhibitor, Cd135 antigen, Fms like tyrosine kinase 3 inhibitor, Hypomethylating agent, Protein inhibitor, Unclassified drug, Aniline derivative, Antineoplastic agent, Benzimidazole derivative, Benzothiazole derivative, Carbanilamide derivative, Carbazole derivative, Crenolanib, Enzyme inhibitor, Flt3 protein, human, Gilteritinib, Lestaurtinib, Midostaurin, Piperidine derivative, Pyrazine derivative, Quizartinib, Acute myeloid leukemia, Adverse outcome, Allogeneic hematopoietic stem cell transplantation, Allogeneic stem cell transplantation, Anemia, Antineoplastic activity, Cancer combination chemotherapy, Cancer prognosis, Cancer survival, Disease association, Drug efficacy, Drug safety, Fever, Flt3 signaling, Gene mutation, Human, Leukemogenesis, Nausea, Priority journal, Protein function, Protein protein interaction, Protein targeting, Rash, Relapse, Review, Risk benefit analysis, Signal transduction, Genetics, Randomized controlled trial (topic), Tumor recurrence