Clinical profile of gilteritinib in Japanese patients with relapsed/refractory acute myeloid leukemia: An open‐label phase 1 study |
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| Authors: | Kensuke Usuki Toru Sakura Yukio Kobayashi Toshihiro Miyamoto Hiroatsu Iida Satoshi Morita Erkut Bahceci Masahito Kaneko Mikiko Kusano Shunsuke Yamada Shigeru Takeshita Shuichi Miyawaki Tomoki Naoe |
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| Affiliation: | 1. NTT Medical Center Tokyo, Tokyo, Japan;2. Saiseikai Maebashi Hospital, Gunma, Japan;3. National Cancer Center, Tokyo, Japan;4. Kyushu University Hospital, Fukuoka, Japan;5. National Hospital Organization Nagoya Medical Center, Nagoya, Japan;6. Kyoto University Hospital, Kyoto, Japan;7. Astellas Pharma Global Development, Inc., Northbrook, IL, USA;8. Astellas Pharma Inc., Tokyo, Japan;9. Tokyo Metropolitan Ohtsuka Hospital, Tokyo, Japan |
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| Abstract: | Gilteritinib, a novel, highly specific, potent fms‐like tyrosine kinase 3/AXL inhibitor, demonstrated antileukemic activity in patients with relapsed/refractory (R/R) acute myeloid leukemia (AML). In this open‐label phase 1 study (NCT02181660), Japanese patients (aged ≥18 years) with R/R AML received once‐daily gilteritinib, escalating from 20 to 300 mg/d. Primary endpoints were safety/tolerability, including the maximum tolerated dose (MTD) and the recommended dose (RD); secondary endpoints were antileukemic activity and pharmacokinetics (PK). Twenty‐four Japanese patients with R/R AML received once‐daily oral gilteritinib in 1 of 6 dose‐escalation cohorts (20, 40, 80, 120, 200, and 300 mg/d). Gilteritinib was well tolerated. The MTD was 200 mg/d; dose‐limiting toxicities were grade 3 tumor lysis syndrome (120 mg/d; n = 1); and grade 3 elevated blood lactate dehydrogenase, amylase, blood creatine phosphokinase levels, and syncope (all n = 2; 300 mg/d). The RD was 120 mg/d. The most common drug‐related grade ≥3 adverse events were thrombocytopenia (n = 4 [16.7%]) and increased blood creatine phosphokinase (n = 3 [12.5%]). Gilteritinib had a dose‐proportional PK profile. Among patients with mutated fms‐like tyrosine kinase 3, the overall response rate (ORR) was 80% (n = 4 of 5; complete remission [CR] with incomplete platelet recovery, 1 [20%]; CR with incomplete hematologic recovery, 2 [40%]; partial remission (PR), 1 [20%]). Among patients with wild‐type fms‐like tyrosine kinase 3, ORR was 36.4%; (n = 4 of 11; CR, 1 [9.1%]; CR with incomplete platelet recovery, 2 [18.2%]; PR, 1 [9.1%]). In conclusion, gilteritinib was well tolerated and demonstrated antileukemic activity in a Japanese R/R AML population. |
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| Keywords: | acute myeloid leukemia bone marrow fms‐like tyrosine kinase 3 hematopoiesis mutation |
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