A phase I/II study of gilteritinib in combination with chemotherapy in newly diagnosed patients with AML in Asia: final analysis.

IF 2.8 3区医学 Q2 HEMATOLOGY

Therapeutic Advances in Hematology Pub Date : 2026-03-11 eCollection Date: 2026-01-01 DOI:10.1177/20406207261419953

Masashi Sawa, Toshihiro Miyamoto, Hee-Je Kim, Yasushi Hiramatsu, June-Won Cheong, Takayuki Ikezoe, Tomoki Naoe, Koichi Akashi, Satoshi Morita, Masanori Kosako, Masaki Shimura, Wataru Terada, Takeshi Kadokura, Jason Hill, Shuichi Miyawaki, Stanley C Gill, Alexandra Heinloth, Nahla Hasabou

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引用次数: 0

Abstract

Background: Mutations in the FMS-like tyrosine kinase 3 (FLT3) gene are present in approximately 30% of patients with newly diagnosed (ND) acute myeloid leukemia (AML), and are associated with worse therapy outcomes compared to the general AML population. Gilteritinib, a selective oral FLT3 inhibitor, is a promising treatment option for this patient population.

Objectives: To assess the safety and efficacy of gilteritinib in combination with induction and consolidation chemotherapy in Asian patients with ND, FLT3-mutated (FLT3 ^mut+) AML.

Design: This study was a phase I/II open-label, single-arm study. Herein, we present the final results from phase II.

Methods: A total of 84 patients were enrolled in 33 centers across Japan, Korea, and Taiwan. All patients enrolled in phase II received induction and consolidation therapy with gilteritinib 120 mg/day plus chemotherapy (induction: ⩽2 cycles, idarubicin/cytarabine once-daily; consolidation: ⩽4 cycles, cytarabine twice-daily) followed by maintenance with gilteritinib 120 mg/day monotherapy (⩽26 cycles). The primary efficacy endpoint was the complete remission (CR) rate after induction therapy.

Results: The primary endpoint of CR rate after induction was 50.0% (90% CI: 40.4-59.6). Gilteritinib in combination with chemotherapy achieved high composite CR (CRc; 86.6%, 95% CI: 77.3-93.1) rates after induction. The overall survival (OS) rate at 3 years was 71.6%, and the median OS was 48.2 months; however, due to the immaturity of the data, the median OS should be interpreted with caution. In addition, 51.2% of patients underwent hematopoietic stem cell transplantation during the study period. The safety profile of gilteritinib was as expected, and no new safety signals were identified.

Conclusion: Induction and consolidation with gilteritinib plus chemotherapy, and maintenance with gilteritinib monotherapy were well tolerated in ND patients in Asia with FLT3 ^mut+ AML and had favorable efficacy compared with historical data.

Trial registration: This trial was registered with the ClinicalTrials.gov identifier NCT02310321.

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gilteritinib联合化疗治疗亚洲新诊断AML患者的I/II期研究：最终分析

背景：fms样酪氨酸激酶3 （FLT3）基因突变存在于大约30%的新诊断（ND）急性髓性白血病（AML）患者中，与普通AML人群相比，与更差的治疗结果相关。Gilteritinib是一种选择性口服FLT3抑制剂，对于这类患者来说是一种很有希望的治疗选择。目的：评估吉特替尼联合诱导和巩固化疗治疗亚洲ND， FLT3突变（FLT3突变+）AML患者的安全性和有效性。设计：本研究为I/II期开放标签单臂研究。在此，我们介绍了第二阶段的最终结果。方法：在日本、韩国和台湾的33个中心共纳入84例患者。所有II期患者均接受吉特替尼120mg /天的诱导和巩固治疗加化疗（诱导：≤2个周期，伊达柔比星/阿糖胞苷每日1次；巩固：≤4个周期，阿糖胞苷每日2次），然后用吉特替尼120mg /天单药治疗维持（≤26个周期）。主要疗效终点为诱导治疗后完全缓解（CR）率。结果：诱导后CR率的主要终点为50.0% （90% CI: 40.4 ~ 59.6）。吉尔替尼联合化疗诱导后获得较高的复合CR （CRc; 86.6%, 95% CI: 77.3-93.1）率。3年总生存率（OS）为71.6%，中位OS为48.2个月；然而，由于数据的不成熟，中位OS应该谨慎解释。此外，51.2%的患者在研究期间接受了造血干细胞移植。gilteritinib的安全性符合预期，没有发现新的安全信号。结论：与历史数据相比，吉特替尼联合化疗诱导和巩固以及吉特替尼单药维持在亚洲FLT3 mut+ AML ND患者中耐受性良好，且疗效良好。试验注册：该试验已注册ClinicalTrials.gov识别码NCT02310321。

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来源期刊

Therapeutic Advances in Hematology HEMATOLOGY-

CiteScore

4.30

自引率

0.00%

发文量

审稿时长

7 weeks

期刊介绍： Therapeutic Advances in Hematology delivers the highest quality peer-reviewed articles, reviews, and scholarly comment on pioneering efforts and innovative studies across all areas of hematology. The journal has a strong clinical and pharmacological focus and is aimed at clinicians and researchers in hematology, providing a forum in print and online for publishing the highest quality articles in this area.