Hematology/oncology clinics of North America
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Hematol. Oncol. Clin. North Am. · Aug 2017
ReviewThe Development of FLT3 Inhibitors in Acute Myeloid Leukemia.
FLT3 mutations, generally associated with a poor prognosis, are found in approximately one-third of patients with acute myeloid leukemia (AML) and represent an attractive therapeutic target. FLT3 inhibitors undergoing clinical evaluation include first-generation relatively non-specific small molecules and second-generation compounds with higher potency and selectivity against mutant FLT3. Recently presented results from a prospective randomized clinical trial will likely lead to a change in the standard of care for younger patients with FLT3-mutated AML: addition of the multi-targeted FLT3 inhibitor midostaurin to standard induction and consolidation chemotherapy. Thus, personalized therapies for this subset of AML will soon be possible.
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Hematol. Oncol. Clin. North Am. · Aug 2017
ReviewMechanisms of Resistance to FLT3 Inhibitors and the Role of the Bone Marrow Microenvironment.
The presence of FLT3 mutations in acute myeloid leukemia (AML) carries a particularly poor prognosis, making the development of FLT3 inhibitors an imperative goal. The last decade has seen an abundance of clinical trials using these drugs alone or in combination with chemotherapy. ⋯ Initial success has been followed by the emergence of clinical resistance. Although novel FLT3 inhibitors are being developed, studies into mechanisms of resistance raise hope of new strategies to prevent emergence of resistance and eliminate minimal residual disease.