CALGB 10603/RATIFY 10-year follow-up: midostaurin versus placebo plus intensive chemotherapy in newly diagnosed FLT3-mutant AML

Data from thePhase III C10603/RATIFY study (NCT00651261) shows that in previously untreated FLT3 mutantacute myeloid leukemia (AML)

Patients (N=717; midostaurin, N=360; placebo, N=357) were stratified according toFLT3 mutation status: ITD allele ratio <0.7 vs ITD allele ratio ≥0.7 vs TKD. The improvement in EFS was sustained for a median of 8.2 months (95% CI, 5.5-11.4) in the midostaurin group compared with 3.0 months (95% CI, 1.9-6.0) in the placebo group (HR, 0.79; 95% CI, 0.67-0.94; p=0.0067).

The 10-year OS estimate for midostaurin was 43.7% (95% CI, 38.7-49.3) compared with 38.6% for placebo (95% CI, 33.6-44.4; p=0.0485), with favorable trends in OS across all three mutation subgroups. Stratification by sex showed that men (p=0.005) maintained the 10-year OS benefit but women (p=0.9) did not, although an EFS benefit was observed in both.

CR1 transplantation was overall very beneficial, with 10-year OS of 56.0% compared with 35.8% without transplantation (p<0.001). Among CR1 patients randomized to maintenance therapy, midostaurin reduced the CIR in ELN 2017 favorable and intermediate-risk patients but not in adverse-risk disease (HR 0.71, 0.47, and 1.01, respectively).

The EFS benefit of midostaurin was maintained over time, while the OS benefit declined, which may be partially attributable to older patients. Patient and disease factors differ between early versus late relapses, suggesting that alternative treatments based on treatment phase may be beneficial.

Reference materials:https://aml-hub.com/medical-information/calgb-10603ratify-10-year-follow-up-midostaurin-vs-placebo-plus-intensive-chemotherapy-in-newly-diagnosed-flt3-mutated-aml