• Thomas Fischer, Richard M Stone, Daniel J Deangelo, Ilene Galinsky, Elihu Estey, Carlo Lanza, Edward Fox, Gerhard Ehninger, Eric J Feldman, Gary J Schiller, Virginia M Klimek, Stephen D Nimer, D Gary Gilliland, Catherine Dutreix, Alice Huntsman-Labed, Jodi Virkus, and Francis J Giles.
• Dana-Farber Cancer Institute, 44 Binney St, Boston, MA 02115, USA.
• J. Clin. Oncol. 2010 Oct 1; 28 (28): 4339-45.

PurposeMutations leading to constitutive activation of the FMS-like tyrosine kinase 3 receptor (FLT3) occur in blasts of 30% of patients with acute myeloid leukemia (AML). Midostaurin (PKC412; N-benzoylstaurosporin) is a multitargeted tyrosine kinase inhibitor, with demonstrated activity in patients with AML/myelodysplastic syndrome (MDS) with FLT3 mutations.Patients And MethodsNinety-five patients with AML or MDS with either wild-type (n = 60) or mutated (n = 35) FLT3 were randomly assigned to receive oral midostaurin at 50 or 100 mg twice daily. The drug was discontinued in the absence of response at 2 months, disease progression, or unacceptable toxicity. Response was defined as complete response, partial response (PR), hematologic improvement, or reduction in peripheral blood or bone marrow blasts by ≥ 50% (BR).ResultsThe rate of BR for the population in whom efficacy could be assessed (n = 92) was 71% in patients with FLT3-mutant and 42% in patients with FLT3 wild-type. One PR occurred in a patient with FLT3-mutant receiving the 100-mg dose regimen. Both doses were well-tolerated; there were no differences in toxicity or response rate according to the dose of midostaurin.ConclusionThese results suggest that midostaurin has hematologic activity in both patients with FLT3-mutant and wild-type. The degree of clinical activity observed supports additional studies that combine midostaurin and other agents such as chemotherapy especially in FLT3-mutant AML.

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