Sawa Masashi, Miyamoto Toshihiro, Kim Hee-Je, Hiramatsu Yasushi, Cheong June-Won, Ikezoe Takayuki, Naoe Tomoki, Akashi Koichi, Morita Satoshi, Kosako Masanori, Ikegaya Moyu, Terada Wataru, Kadokura Takeshi, Hill Jason, Miyawaki Shuichi, Gill Stanley C, Heinloth Alexandra, Hasabou Nahla
Department of Hematology and Oncology, Aichi, Japan.
Department of Hematology, Kanazawa University, Ishikawa, Japan.
Int J Hematol. 2025 Jan;121(1):56-67. doi: 10.1007/s12185-024-03840-x. Epub 2024 Nov 6.
This interim analysis of a phase 1/2, open-label, single-arm study assessed the safety, efficacy, and pharmacokinetics of gilteritinib plus chemotherapy in adults with newly diagnosed FLT3 mutation-positive acute myeloid leukemia.
In sequential phase 1 and 2 studies, induction and consolidation therapy with gilteritinib 120 mg/day plus chemotherapy (induction: idarubicin/cytarabine once daily; consolidation: cytarabine twice daily) was followed by maintenance gilteritinib 120 mg/day monotherapy. Endpoints included maximum tolerated dose (MTD), recommended expansion dose (RED), and dose-limiting toxicity (phase 1), and complete remission (CR) rate following induction therapy (primary endpoint), overall survival (OS), safety, and pharmacokinetics (phase 2).
In phase 1, MTD was not reached and RED was 120 mg/day. In phase 2, the CR rate was 50.0% after induction (90% confidence interval [CI] 40.4, 59.6); however, the lower confidence limit did not exceed the pre-defined 55% benchmark. Composite CR (CRc) rates were high following induction (86.6%, 95% CI [77.3, 93.1]), consolidation, and maintenance therapy (87.8%, 95% CI [78.7, 94.0], each). The probability of OS was 86.6% at 12 months. No new safety findings were reported.
In this interim analysis, gilteritinib 120 mg/day in combination with chemotherapy was well tolerated, with similar CRc rates to previous studies.
本1/2期开放标签单臂研究的中期分析评估了吉瑞替尼联合化疗在新诊断的FLT3突变阳性急性髓系白血病成人患者中的安全性、疗效和药代动力学。
在1期和2期序贯研究中，先采用吉瑞替尼120mg/天联合化疗进行诱导和巩固治疗（诱导：阿糖胞苷/柔红霉素每日1次；巩固：阿糖胞苷每日2次），随后采用吉瑞替尼120mg/天单药维持治疗。终点包括最大耐受剂量（MTD）、推荐扩展剂量（RED）和剂量限制毒性（1期），以及诱导治疗后的完全缓解（CR）率（主要终点）、总生存期（OS）、安全性和药代动力学（2期）。
在1期，未达到MTD，RED为120mg/天。在2期，诱导治疗后的CR率为50.0%（90%置信区间[CI]40.4，59.6）；然而，较低的置信下限未超过预先定义的55%基准。诱导、巩固和维持治疗后的复合CR（CRc）率均较高（分别为86.6%，95%CI[77.3，93.1]；87.8%，95%CI[78.7，94.0]）。12个月时OS概率为86.6%。未报告新的安全性发现。
在本次中期分析中，吉瑞替尼120mg/天联合化疗耐受性良好，CRc率与既往研究相似。
