TY - JOUR
T1 - Gilteritinib or chemotherapy for relapsed or refractory FLT3-mutated AML
AU - Perl, Alexander E.
AU - Martinelli, Giovanni
AU - Cortes, Jorge E.
AU - Neubauer, Andreas
AU - Berman, Ellin
AU - Paolini, Stefania
AU - Montesinos, Pau
AU - Baer, Maria R.
AU - Larson, Richard A.
AU - Ustun, Celalettin
AU - Fabbiano, Francesco
AU - Erba, Harry P.
AU - Di Stasi, Antonio
AU - Stuart, Robert
AU - Olin, Rebecca
AU - Kasner, Margaret
AU - Ciceri, Fabio
AU - Chou, Wen Chien
AU - Podoltsev, Nikolai
AU - Recher, Christian
AU - Yokoyama, Hisayuki
AU - Hosono, Naoko
AU - Yoon, Sung Soo
AU - Lee, Je Hwan
AU - Pardee, Timothy
AU - Fathi, Amir T.
AU - Liu, Chaofeng
AU - Hasabou, Nahla
AU - Liu, Xuan
AU - Bahceci, Erkut
AU - Levis, Mark J.
N1 - Publisher Copyright:
Copyright © 2019 Massachusetts Medical Society.
PY - 2019/10/31
Y1 - 2019/10/31
N2 - 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.
AB - 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.
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U2 - 10.1056/NEJMoa1902688
DO - 10.1056/NEJMoa1902688
M3 - Article
C2 - 31665578
AN - SCOPUS:85074388201
SN - 0028-4793
VL - 381
SP - 1728
EP - 1740
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 18
ER -