Adding midostaurin to standard chemotherapy improves outcomes for AML patients with a FLT3 mutation

This study examined the benefits of adding midostaurin (Rydapt) to standard chemotherapy in patients with acute myeloid leukemia (AML) and a genetic abnormality on the FLT3 gene. Authors reported improved treatment outcomes when AML patients with the FLT3 mutation were also treated with midostaurin.

AML is cancer of the blood and bone marrow. Certain genetic changes in AML can make it more difficult to treat. About 30% of adults with newly diagnosed AML show a duplication (a type of mutation) on the fms-related tyrosine kinase 3 (FLT3) gene. Patients with the FLT3 mutation often have a poor prognosis. It has been suggested that adding midostaurin to standard treatment with chemotherapy may improve outcomes. Midostaurin is a type of targeted therapy that uses substances to identify and attack specific cancer cells with less harm to normal cells.

The aim of this study was to examine the benefits of adding midostaurin to standard treatment in AML patients with a FLT3 mutation.

3,277 adults with newly diagnosed AML were screened for the FLT3 mutation. 896 patients (27%) tested positive. Of these, 717 participated in the study. Patients were randomly assigned to receive either standard chemotherapy plus midostaurin or standard chemotherapy plus placebo (control drug with no active effect). Standard chemotherapy consisted of daunorubicin (Cerubidine) and cytarabine (Cytosar-U), followed by high-dose cytarabine.

There were no significant differences in age, gender, ethnicity, FLT3 subtype, blood counts, and disease stage between treatment groups.

Overall survival (time from treatment until death from any cause) was significantly longer among patients treated with midostaurin. Average overall survival was 74.7 months in the midostaurin group and 25.6 months in the placebo group. The 4-year overall survival rate was 51.4% in the midostaurin group and 44.3% in the placebo group. Average disease-free survival was 26.7 months in the midostaurin group and 15.5 months in the placebo group.

The risk of treatment-related events such as disease progression or death was reduced by 21.6% among patients treated with midostaurin. 28.2% of patients in the midostaurin group were event-free at 4 years. This was significantly greater compared to 20.6% in the placebo group.

Complete remission was observed in 58.9% of patients in the midostaurin group and in 53.5% of patients in the placebo group. This difference was not statistically significant.

The rate of serious side effects was similar between groups. Blood-related side effects (such as low platelet levels [blood cells involved in clotting] or low white blood cell counts) were some of the most common side effects. These occurred in up to 97% of patients. The rates were similar between groups. Only anemia (low red blood cells) was significantly more common among patients treated with midostaurin. Other common side effects included fever (reported in 82% of patients), infection (50 to 52%), and diarrhea (15 to 16%).

Authors concluded that midostaurin improves overall survival and event-free survival in AML patients with a FLT3 mutation.

Some of the authors are affiliated with manufacturers of the drugs used in this study.