Adding midostaurin, a multitargeted kinase inhibitor, to standard chemotherapy provides significant survival benefit for patients with acute myeloid leukemia (AML) and a FLT3 mutation, a study published in the New England Journal of Medicine has shown.

Because the prognosis for patients with AML and a FLT3 mutation is poor, investigators led by Richard M. Stone, MD, of the Dana Farber Cancer Institute, in Boston, sought to determine if the addition of midostaurin, an oral multitargeted kinase inhibitor that is active in patients with a FLT3 mutation, would improve overall survival in this population.

For the study, patients, aged 18 to 59 years, with newly diagnosed acute myeloid leukemia were screened for the FLT3 mutation. Other criteria for inclusion in the study population included: AML was not therapy-related, bilirubin level was less than 2.5 × the upper limit of normal (ULN), and had no other major coexisting illnesses. Those on hydroxyurea therapy for 5 days before the start of the trial were eligible, as well as those who had undergone allogeneic transplantation.

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All eligible patients (N=717) received standard chemotherapy consisting of induction therapy with daunorubicin and cytarabine and consolidation therapy with high-dose cytarabine, In addition, they were randomly assigned to receive midostaurin (n=360) or placebo (n=357).

Randomization was stratified according to FLT3 mutation subtype: TKD (162 patients) or ITD mutation with either a high ratio (greater than 0.7) or a low ratio (0.05 to 0.7) of mutant to wild-type alleles (ITD [high] or ITD [low], 214 patients and 341 patients, respectively).

The treatment groups were well balanced with respect to age, race, FLT3 subtype, cytogenetic risk, and blood counts. However, the groups did not match in sex; 51.7% of patients in the midostaurin group were women vs 59.4% in the placebo group (P =.04).

Patients in the midostaurin group experienced significantly longer overall survival than those in the placebo group (hazard ratio [HR] for death, 0.78; one-sided P =.009). Event-free survival was also longer for the midostaurin group vs the placebo group (HR for event or death, 0.78; one-sided P =.002). In both the primary analysis and an analysis in which data for patients who underwent transplantation were censored, the benefit of midostaurin was consistent across the 3 subtypes of FLT3 mutation. Severe adverse events were similar in the groups.

The addition of midostaurin to standard chemotherapy significantly prolongs overall survival and event-free survival in patients with AML and a FLT3 mutation, the investigators concluded.


1. Stone RM, Mandrekar SJ, Sanford BL, et al. Midostaurin plus chemotherapy for acute myeloid leukemia with a FLT3 mutation [published online June 23, 2017]. N Engl J Med. doi: 10.1056/NEJM0a1614359