Gilteritinib or Chemotherapy for Relapsed or Refractory FLT3 -Mutated AML
Open accessAbstract
BACKGROUNDPatients with relapsed or refractory acute myeloid leukemia (AML) with mutations in the FMS-like tyrosine kinase 3 gene (FLT3) infrequently have a response to salvage chemotherapy.Gilteritinib is an oral, potent, selective FLT3 inhibitor with single-agent activity in relapsed or refractory FLT3-mutated AML. METHODSIn a phase 3 trial, we randomly assigned adults with relapsed or refractory FLT3mutated AML in a 2:1 ratio to receive either gilteritinib (at a dose of 120 mg per day) or salvage chemotherapy.The two primary end points were overall survival and the percentage of patients who had complete remission with full or partial hematologic recovery.Secondary end points included event-free survival (freedom from treatment failure [i.e., relapse or lack of remission] or death) and the percentage of patients who had complete remission. RESULTSOf 371 eligible patients, 247 were randomly assigned to the gilteritinib group and 124 to the salvage chemotherapy group.The median overall survival in the gilteritinib group was significantly longer than that in the chemotherapy group (9.3 months vs. 5.6 months; hazard ratio for death, 0.64; 95% confidence interval [CI], 0.49 to 0.83; P<0.001).The median event-free survival was 2.8 months in the gilteritinib group and 0.7 months in the chemotherapy group (hazard ratio for treatment failure or death, 0.79; 95% CI, 0.58 to 1.09).The percentage of patients who had complete remission with full or partial hematologic recovery was 34.0% in the gilteritinib group and 15.3% in the chemotherapy group (risk difference, 18.6 percentage points; 95% CI, 9.8 to 27.4); the percentages with complete remission were 21.1% and 10.5%, respectively (risk difference, 10.6 percentage points; 95% CI, 2.8 to 18.4).In an analysis that was adjusted for therapy duration, adverse events of grade 3 or higher and serious adverse events occurred less frequently in the gilteritinib group than in the chemotherapy group; the most common adverse events of grade 3 or higher in the gilteritinib group were febrile neutropenia (45.9%), anemia (40.7%), and thrombocytopenia (22.8%). CONCLUSIONSGilteritinib resulted in significantly longer survival and higher percentages of patients with remission than salvage chemotherapy among patients with relapsed or refractory FLT3-mutated AML.(Funded by Astellas Pharma; ADMIRAL ClinicalTrials .govnumber, NCT02421939.
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FLT3 inhibitors improve the survival of patients with acute myeloid leukaemia.
“There are FLT3 inhibitors that improve the survival of patients with acute myeloid leukaemia49,50.”
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- Authors
- Perl, A. E., Martinelli, G., Cortes, J. E., Neubauer, A., Berman, E., Paolini, S., Montesinos, P., Baer, M. R., Larson, R. A., Ustun, C., Fabbiano, F., Erba, H. P., Di Stasi, A., Stuart, R., Olin, R., Kasner, M., Ciceri, F., Chou, W.-C., Podoltsev, N., Recher, C., Yokoyama, H., Hosono, N., Yoon, S.-S., Lee, J.-H., Pardee, T., Fathi, A. T., Liu, C., Hasabou, N., Liu, X., Bahceci, E., & Levis, M. J.
- Affiliations
- Thomas Jefferson University (US)
- From the Abramson Cancer Center, University of Pennsylvania (A.E.P.), and Thomas Jefferson University (M.K.) — both in Philadelphia; Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Istituto Di Ricovero e Cura a Carattere Scientifico (IRCCS), Meldola (G.M.), L. and A. Seràgnoli Institute of Hematology, Bologna University Medical School, Bologna (S.P.), Ospedali Riuniti Villa Sofia-Cervello, Palermo (F.F.), and IRCCS San Raffaele Scientific Institute, Milan (F.C.) — all in Italy;...
- Memorial Sloan Kettering Cancer Center (US)
- University of Fukui (JP)
- Seoul National University (KR)
- Atrium Health Wake Forest Baptist (US)
- Harvard University (US)
- Johns Hopkins University (US)
- ORCID
- Perl, Alexander E.
- Martinelli, Giovanni
- Neubauer, Andreas
- Berman, Ellin
- Paolini, Stefania
- Montesinos, Pau
- Baer, Maria R.
- Larson, Richard A.
- Erba, Harry P.
- Stuart, Robert
- Olin, Rebecca
- Kasner, Margaret
- Ciceri, Fabio
- Chou, Wen-Chien
- Podoltsev, Nikolai
- Yokoyama, Hisayuki
- Hosono, Naoko
- Yoon, Sung-Soo
- Lee, Je-Hwan
- Pardee, Timothy
- Fathi, Amir T.
- Liu, Chaofeng
- Liu, Xuan
- Levis, Mark J.
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2019-10-31
- Volume
- 381
- Issue
- 18
- Pages
- 1728-1740
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2982353618
- Cited by
- 1,287
- References
- 4
- Citations by year
- 2026: 140 · 2025: 163 · 2024: 190 · 2023: 184 · 2022: 233 · 2021: 212 · 2020: 157 · 2019: 8
- FWCI
- 107.96
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- The Medicine Forum (submittedVersion)
- Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
- Funders
- Astellas Pharma US
- Topics
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
- Health Sciences › Medicine › Hematology › Chronic Myeloid Leukemia Treatments
- Keywords
- gilteritinib, FLT3-mutated acute myeloid leukemia, relapsed/refractory AML, salvage chemotherapy, FLT3 inhibitors, overall survival, event-free survival, complete remission, adverse events, hypomethylating agents, allogeneic stem cell transplantation
- MeSH terms
- Administration, Oral, Adult, Aged, Aged, 80 and over, Aniline Compounds, Antineoplastic Agents, Antineoplastic Combined Chemotherapy Protocols, Female, Follow-Up Studies, Humans, Liver, Male, Middle Aged, Mutation, Pyrazines, Recurrence, Remission Induction, Leukemia, Myeloid, Acute, Survival Analysis, Salvage Therapy, Drug Resistance, Neoplasm, fms-Like Tyrosine Kinase 3
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