NEW ORLEANS—For patients with acute myeloid leukemia (AML) whose blasts have FLT-3 mutations, the multitargeted kinase inhibitor midostaurin produced an encouraging overall survival rate of 85% at one year and 62% at two years, according to the results of a Phase Ib trial from Dana-Farber Cancer Institute reported here at the ASH Annual Meeting. The drug is known to have clinical activity in FLT3-mutant and FLT3-wild-type AML, but until now has only rarely shown complete remissions, said the researchers, led by Richard M. Stone, MD.
Since preclinical studies demonstrated synergy between FLT3 inhibitors and chemotherapy, the clinical trial was developed to investigate the feasibility of administering oral midostaurin along with daunorubicin and cytarabine as induction and high-dose cytarabine as post-remission therapy in newly diagnosed patients younger than age 61 with de novo AML.
The 40 patients in the study received midostaurin at a dose of 50 mg, and complete responses were seen in 32 of the patients (80%), including 20 of the 27 with wild-type FLT3 (74%) and 12 of the 13 FLT3-mutant patients (92%).
“Even accounting for their differing cytogenetics and ages, the overall survival of the FLT3-mutant subgroup was expected to be inferior to that of the FLT3 wild-type subgroup,” Dr. Stone said. “However, we report that the one- and two-year overall survival rates for patients with FLT3-mutant AML were 85% and 62%, respectively, and were comparable to that of the FLT3-wild type subgroup, at 81% and 59% respectively.”
He said that although these data are based on small numbers and not stratified for the type of FLT3 mutation, the long-term results do suggest that combination therapy with a FLT3 inhibitor and chemotherapy might be effective enough to obviate the perceived need for allogeneic stem cell transplantation for FLT3-mutant AML patients in first complete remission.
Moreover, he and his colleagues said, the results support the rationale for the ongoing international Phase III study of induction, post-remission intensification, and maintenance with midostaurin (at a dose of 50 mg po bid) or placebo.