Gilteritinib或化療治療復發或難治性FLT3突變的AML
作者：
小柯機器人發布時間：2019/11/4 10:06:08
復發或難治性急性髓系白血病（AML）患者中，FMS樣酪氨酸激酶3基因（FLT3）突變型很少會對挽救性化療有反應。Gilteritinib是一類口服的、有效的、選擇性的FLT3抑制劑，在復發或難治性FLT3突變的AML中具有一定的單藥活性。
在這項臨床3期的試驗中，研究組共招募了371名復發或難治性FLT3突變的AML患者，將其按2：1隨機分為兩組，其中247名接受Gilteritinib（每天120mg）口服，124名接受挽救性化療。
Gilteritinib組的中位總生存期為9.3個月，顯著長於化療組（5.6個月）。Gilteritinib組的中位無事件生存期為2.8個月，顯著長於對照組（0.7個月）。Gilteritinib組血液學完全或部分恢復的完全緩解患者所佔比率為34.0%，化療組為15.3%；兩組的完全緩解率分別為21.1%和10.5%。根據治療時間進行校正後，Gilteritinib組3級及以上不良事件及嚴重不良事件的發生率均顯著低於化療組，其中最常見的不良事件為發熱性中性粒細胞減少（45.9%）、貧血（40.7%）和血小板減少（22.8%）。
綜上，對於復發或難治性FLT3突變的AML患者，與挽救性化療相比，Gilteritinib可顯著延長患者的生存期，提高緩解率。
附：英文原文
Title: Gilteritinib or Chemotherapy for Relapsed or Refractory FLT3-Mutated AML
Author: Alexander E. Perl, M.D.,, Giovanni Martinelli, M.D.,, Jorge E. Cortes, M.D.,, Andreas Neubauer, M.D.,, Ellin Berman, M.D.,, Stefania Paolini, M.D., Ph.D.,, Pau Montesinos, M.D.,, Maria R. Baer, M.D.,, Richard A. Larson, M.D.,, Celalettin Ustun, M.D.,, Francesco Fabbiano, M.D.,, Harry P. Erba, M.D., Ph.D.,, Antonio Di Stasi, M.D.,, Robert Stuart, M.D.,, Rebecca Olin, M.D.,, Margaret Kasner, M.D.,, Fabio Ciceri, M.D.,, Wen-Chien Chou, M.D., Ph.D.,, Nikolai Podoltsev, M.D.,, Christian Recher, M.D.,, Hisayuki Yokoyama, M.D.,, Naoko Hosono, M.D., Ph.D.,, Sung-Soo Yoon, M.D., Ph.D.,, Je-Hwan Lee, M.D., Ph.D.,, Timothy Pardee, M.D., Ph.D.,, Amir T. Fathi, M.D.,, Chaofeng Liu, Ph.D.,, Nahla Hasabou, M.D.,, Xuan Liu, Ph.D.,, Erkut Bahceci, M.D.,, and Mark J. Levis, M.D., Ph.D.
Issue&Volume: 2019-10-30
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 FLT3-mutated 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.
DOI: NJ201910313811808
Source: https://www.nejm.org/doi/full/10.1056/NEJMoa1902688