Gilteritinib or chemotherapy for relapsed or refractory FLT3-mutated AML
Journal
New England Journal of Medicine
Journal Volume
381
Journal Issue
18
Pages
1728-1740
Date Issued
2019
Author(s)
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.
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.
Abstract
BACKGROUND Patients 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. METHODS In 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. RESULTS Of 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%). CONCLUSIONS Gilteritinib resulted in significantly longer survival and higher percentages of patients with remission than salvage chemotherapy among patients with relapsed or refractory FLT3-mutated AML. Copyright ? 2019 Massachusetts Medical Society.
SDGs
Other Subjects
alanine aminotransferase; alkaline phosphatase; azacitidine; CD135 antigen; cytarabine; etoposide; fludarabine; gilteritinib; granulocyte colony stimulating factor; idarubicin; midostaurin; mitoxantrone; aniline derivative; antineoplastic agent; CD135 antigen; gilteritinib; pyrazine derivative; acute myeloid leukemia; adult; aged; alanine aminotransferase blood level; alkaline phosphatase blood level; anemia; Article; cancer chemotherapy; cancer recurrence; cancer regression; cancer risk; cause of death; constipation; controlled study; coughing; drug dose escalation; drug efficacy; drug safety; dyspnea; event free survival; fatigue; febrile neutropenia; female; fever; FLT3 gene; gene mutation; genetic association; hazard ratio; headache; human; hypokalemia; low drug dose; major clinical study; male; multiple cycle treatment; overall survival; peripheral edema; phase 3 clinical trial; platelet count; priority journal; randomized controlled trial; salvage therapy; side effect; thrombocytopenia; treatment duration; treatment failure; treatment response; vomiting; acute myeloid leukemia; clinical trial; comparative study; drug effect; drug resistance; follow up; genetics; liver; middle aged; mortality; multicenter study; mutation; oral drug administration; recurrent disease; remission; salvage therapy; survival analysis; very elderly; Administration, Oral; Adult; Aged; Aged, 80 and over; Aniline Compounds; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Drug Resistance, Neoplasm; Female; fms-Like Tyrosine Kinase 3; Follow-Up Studies; Humans; Leukemia, Myeloid, Acute; Liver; Male; Middle Aged; Mutation; Pyrazines; Recurrence; Remission Induction; Salvage Therapy; Survival Analysis
Type
journal article