Acute myeloid leukemia (AML) is an aggressive hematologic malignancy, which is characterized by impaired differentiation and uncontrollable proliferation of myeloid progenitor cells in the bone marrow. One-third of patients with AML have a mutation in the FMS-like tyrosine kinase 3 (FLT3) gene. The FLT3 mutation most commonly occurs as an internal tandem duplication (ITD) and is associated with a poor prognosis. Patients with FLT3-ITD mutated AML are able to achieve complete remission at the same rate as patients with wild-type FLT3 but face a higher relapse rate and reduced overall survival.
The standard treatment for FLT3-ITD mutated AML has been intensive chemotherapy with or without hematopoietic stem cell transplantation (HSCT). In recent years, there has been an emergence of various targeted first and second generation FLT3 inhibitors. The first-generation inhibitors lack specificity for FLT3 and include sunitinib,
sorafenib, lestaurtinib and midostaurin. The second-generation inhibitors potently target
FLT3 and include quizartinib, crenolanib and gilteritinib. Currently, midostaurin is the only FLT3 inhibitor that has been approved by the FDA to treat patients with AML.
A barrier in AML treatment is drug resistance, which can lead to either a lack of efficacy or loss of prior efficacy. There are a variety of intrinsic and extrinsic mechanisms that underlie the acquisition of resistance. This literature review will explore the clinical implications and limitations of the treatment options for patients with FLT3- ITD mutated AML and discuss the negative impact that resistance has on efficacy.
| Identifer | oai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/32984 |
| Date | 24 October 2018 |
| Creators | Argetsinger, Stephanie |
| Contributors | MacNeil, Maryann |
| Source Sets | Boston University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
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