For the remaining patients, 7 þ 3 þ midostaurin is recommended if they are FLT3-ITD or FLT3-TKD positive.

Treatment strategies…Intermediate-risk cytogenetics and FLT3-mutated (ITD or TKD)...Standard-dose cytarabine 200 mg/m2 continuous infusion x 7 days with daunorubicin 60 mg/m2 x 3 days and oral midostaurin 50 mg every 12 hours, days 8-21 (FLT3-mutated AML)

Pts must start their first induction cycle with 7+3 (cytarabine [Ara-C] 100-200 mg/m2/d on days 1-7 + daunorubicin 60-90 mg/m2/d or idarubicin...Most pts had a FLT3-ITD mutation (82.7%), with 17.6% having a FLT3-TKD mutation...242 pts achieved CR/CRi (80.7%)....Midostaurin plus CT resulted in high response rates regardless of pt age, sex, induction drug, or alternative CT regimen.

...AML diagnosis, documented FLT3 mutation (ITD and/or TKD). Patients aged ≥18 years received midostaurin with 1-2 cycles of induction therapy (cytarabine plus daunorubicin or idarubicin) and ≤4 cycles of high-dose cytarabine consolidation chemotherapy or as single-agent maintenance therapy.

Patients were randomly assigned to receive standard chemotherapy (induction therapy with daunorubicin and cytarabine...The FLT3 subtype was ITD (high) in 214 patients, ITD (low) in 341 patients, and TKD in 162 patients. The treatment groups were well balanced with respect to age, race, FLT3 subtype, cytogenetic risk, and blood counts but not with respect to sex (51.7% in the midostaurin group vs. 59.4% in the placebo group were women, P=0.04). Overall survival was significantly longer in the midostaurin group than in the placebo group (hazard ratio for death, 0.78; one-sided P=0.009), as was event-free survival (hazard ratio for event or death, 0.78; one-sided P=0.002). 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 all FLT3 subtypes. The rate of severe adverse events was similar in the two groups.

...Patients must have a documented FLT3 mutation (ITD or TKD).)...

Twenty-six patients were included in the final analysis. Patient characteristics are outlined in TABLE 1. All patients were FLT3 mutated, as confirmed with molecular studies. The FLT3 subtype was ITD (high) in 3 patients, ITD (low) in 16 patients, TKD in 5 patients, and both in 2 patients....Also, CR/CRi rates were higher than previously reported, suggesting that the combination of HD daunorubicin and midostaurin may improve the outcomes of patients with FLT3 mutated AML.