# ADMIRAL: gilteritinib pills versus chemotherapy for relapsed FLT3-mutated acute myeloid leukaemia

Source: https://onco.cc/key-papers/paper-admiral-gilteritinib-flt3-nejm-2019/  
OnCo record `paper-admiral-gilteritinib-flt3-nejm-2019` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

An oral FLT3 inhibitor extended survival compared with salvage chemotherapy in relapsed AML with a FLT3 mutation, doubling the remission rate.

## Summary

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.

## Fields

- Kind: Key paper
- Last checked: 2026-09-08
- Journal: New England Journal of Medicine
- Year: 2019
- DOI: 10.1056/NEJMoa1902688
- Authors: Perl AE, Martinelli G, Cortes JE, et al.
- Findings: 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.
- What it means: 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.
- Caveats: 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.

## Sources

- Full text (DOI): https://doi.org/10.1056/NEJMoa1902688
- ClinicalTrials.gov NCT02421939: https://clinicaltrials.gov/study/NCT02421939

## Connected records

- key papers: [QuANTUM-First: quizartinib added to intensive chemotherapy and continued as maintenance in newly diagnosed FLT3-ITD AML](https://onco.cc/key-papers/paper-quantum-first-quizartinib-lancet-2023/)
- cancers: [Acute myeloid leukaemia](https://onco.cc/cancers/aml/), [FLT3-mutated acute myeloid leukaemia](https://onco.cc/cancers/aml-flt3/)
- technologies: [Allogeneic stem cell transplantation](https://onco.cc/technologies/allogeneic-hsct/)
- targets: [FLT3](https://onco.cc/targets/flt3/)
- drugs: [Gilteritinib](https://onco.cc/drugs/gilteritinib/), [Midostaurin](https://onco.cc/drugs/midostaurin/), [Quizartinib](https://onco.cc/drugs/quizartinib/)
- companies: [Astellas](https://onco.cc/companies/astellas/)
- terms: [Overall survival (OS)](https://onco.cc/terms/os/)
- trials: [ADMIRAL](https://onco.cc/trials/admiral/)
- bottlenecks: [Acquired resistance to every therapy](https://onco.cc/bottlenecks/b-resistance/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)
- people: [Alexander E. Perl](https://onco.cc/people/alexander-perl/)

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