International Journal of Clinical Oncology ( IF 3.3 ) Pub Date : 2021-08-07 , DOI: 10.1007/s10147-021-02006-7 Naoko Hosono 1 , Hisayuki Yokoyama 2, 3 , Nobuyuki Aotsuka 4 , Kiyoshi Ando 5 , Hiroatsu Iida 6 , Takayuki Ishikawa 7 , Kensuke Usuki 8 , Masahiro Onozawa 9 , Masahiro Kizaki 10 , Kohmei Kubo 11 , Junya Kuroda 12 , Yukio Kobayashi 13 , Takayuki Shimizu 14 , Shigeru Chiba 15 , Miho Nara 16 , Tomoko Hata 17 , Michihiro Hidaka 18 , Shin-Ichiro Fujiwara 19 , Yoshinobu Maeda 20 , Yasuyoshi Morita 21 , Mikiko Kusano 22 , Qiaoyang Lu 23 , Shuichi Miyawaki 24 , Erhan Berrak 23 , Nahla Hasabou 23 , Tomoki Naoe 6
Background
Until recently, no effective targeted therapies for FLT3-mutated (FLT3mut+) relapsed/refractory (R/R) acute myeloid leukemia (AML) were available in Japan. The FLT3 inhibitor, gilteritinib, was approved in Japan for patients with FLT3mut+ R/R AML based on the phase 3 ADMIRAL trial, which demonstrated the superiority of gilteritinib over salvage chemotherapy (SC) with respect to overall survival (OS; median OS, 9.3 vs 5.6 months, respectively; hazard ratio, 0.64 [95% confidence interval 0.49, 0.83]; P < 0.001).
Methods
We evaluated the Japanese subgroup (n = 48) of the ADMIRAL trial, which included 33 patients randomized to 120-mg/day gilteritinib and 15 randomized to SC.
Results
Median OS was 14.3 months in the gilteritinib arm and 9.6 months in the SC arm. The complete remission/complete remission with partial hematologic recovery rate was higher in the gilteritinib arm (48.5%) than in the SC arm (13.3%). After adjustment for drug exposure, fewer adverse events (AEs) occurred in the gilteritinib arm than in the SC arm. Common grade ≥ 3 AEs related to gilteritinib were febrile neutropenia (36%), decreased platelet count (27%), and anemia (24%).
Conclusion
Findings in Japanese patients are consistent with those of the overall ADMIRAL study population.
中文翻译:
吉尔特替尼与化疗在日本 FLT3 突变复发/难治性急性髓系白血病患者中的比较
背景
直到最近,日本还没有针对FLT3突变 ( FLT3 mut+)复发/难治性 (R/R) 急性髓系白血病 (AML) 的有效靶向疗法。基于 ADMIRAL 3 期试验,FLT3 抑制剂 gilteritinib 在日本被批准用于FLT3 mut+ R/R AML患者,该试验证明了 gilteritinib 在总生存率(OS;中位 OS,分别为 9.3 个月和 5.6 个月;风险比为 0.64 [95% 置信区间 0.49, 0.83];P < 0.001)。
方法
我们评估了 ADMIRAL 试验的日本亚组 ( n = 48),其中包括随机分配至 120 毫克/天 gilteritinib 的 33 名患者和随机分配至 SC 的 15 名患者。
结果
gilteritinib 组的中位 OS 为 14.3 个月,SC 组为 9.6 个月。gilteritinib 组的完全缓解/完全缓解和部分血液学恢复率(48.5%)高于 SC 组(13.3%)。调整药物暴露后,gilteritinib 组发生的不良事件 (AE) 少于 SC 组。与 gilteritinib 相关的常见 3 级 AE 为发热性中性粒细胞减少症 (36%)、血小板计数减少 (27%) 和贫血 (24%)。
结论
日本患者的结果与整个 ADMIRAL 研究人群的结果一致。