ADMIRAL: gilteritinib pills versus chemotherapy for relapsed FLT3-mutated acute myeloid leukaemia
An oral FLT3 inhibitor extended survival compared with salvage chemotherapy in relapsed AML with a FLT3 mutation, doubling the remission rate.
ADMIRAL randomised 371 adults with relapsed or refractory FLT3-mutated AML in a 2:1 ratio to gilteritinib 120 mg daily or investigator-chosen salvage chemotherapy (high- or low-intensity). Primary endpoints were overall survival and the rate of complete remission or remission with partial haematological recovery. Median OS was 9.3 versus 5.6 months (hazard ratio 0.64) and one-year survival 37.1% versus 16.7%; CR/CRh was 34.0% versus 15.3%. More patients on gilteritinib proceeded to transplant, and toxicity was lower than with chemotherapy. It established single-agent targeted therapy as a standard in relapsed FLT3-mutated AML.
- 371 patients with relapsed/refractory FLT3-mutated AML; gilteritinib vs salvage chemotherapy (2:1).
- Median OS 9.3 vs 5.6 months; hazard ratio 0.64.
- 1-year overall survival 37.1% vs 16.7%.
- CR/CRh 34.0% vs 15.3%; complete remission 21.1% vs 10.5%.
- Fewer grade 3 or higher adverse events per exposure-adjusted analysis with gilteritinib.
ADMIRAL showed that a targeted oral drug can beat chemotherapy outright in relapsed AML, and made gilteritinib the standard bridge to transplant for FLT3-mutated relapse. Its success also underpinned FLT3 inhibitor use in first-line combinations. Resistance through FLT3-independent clones and RAS pathway mutations limits durability without transplant.
- Modest absolute survival gain; most patients not transplanted eventually relapsed.
- Open-label with heterogeneous chemotherapy comparators.
- Excluded patients previously treated with certain FLT3 inhibitors; prior midostaurin exposure was uncommon.
- Differentiation syndrome and QT prolongation require monitoring.