Gilteritinib versus chemotherapy in Japanese patients with FLT3-mutated relapsed/refractory acute myeloid leukemia

Naoko Hosono; Hisayuki Yokoyama; Nobuyuki Aotsuka; Kiyoshi Ando; Hiroatsu Iida; Takayuki Ishikawa; Kensuke Usuki; Masahiro Onozawa; Masahiro Kizaki; Kohmei Kubo; Junya Kuroda; Yukio Kobayashi; Takayuki Shimizu; Shigeru Chiba; Miho Nara; Tomoko Hata; Michihiro Hidaka; Shin-Ichiro Fujiwara; Yoshinobu Maeda; Yasuyoshi Morita; Mikiko Kusano; Qiaoyang Lu; Shuichi Miyawaki; Erhan Berrak; Nahla Hasabou; Tomoki Naoe

doi:10.1007/s10147-021-02006-7

Gilteritinib versus chemotherapy in Japanese patients with FLT3-mutated relapsed/refractory acute myeloid leukemia

Int J Clin Oncol. 2021 Nov;26(11):2131-2141. doi: 10.1007/s10147-021-02006-7. Epub 2021 Aug 7.

Authors

Naoko Hosono¹, Hisayuki Yokoyama^{2

3}, Nobuyuki Aotsuka⁴, Kiyoshi Ando⁵, Hiroatsu Iida⁶, Takayuki Ishikawa⁷, Kensuke Usuki⁸, Masahiro Onozawa⁹, Masahiro Kizaki¹⁰, Kohmei Kubo¹¹, Junya Kuroda¹², Yukio Kobayashi¹³, Takayuki Shimizu¹⁴, Shigeru Chiba¹⁵, Miho Nara¹⁶, Tomoko Hata¹⁷, Michihiro Hidaka¹⁸, Shin-Ichiro Fujiwara¹⁹, Yoshinobu Maeda²⁰, Yasuyoshi Morita²¹, Mikiko Kusano²², Qiaoyang Lu²³, Shuichi Miyawaki²⁴, Erhan Berrak²³, Nahla Hasabou²³, Tomoki Naoe⁶

Affiliations

¹ Department of Hematology and Oncology, Faculty of Medical Sciences, University of Fukui, Fukui, 910-1193, Japan. [email protected].
² Sendai Medical Center, Sendai, Japan.
³ Tohoku University, Sendai, Japan.
⁴ Japanese Red Cross Narita Hospital, Narita, Japan.
⁵ Tokai University School of Medicine, Isehara, Japan.
⁶ NHO Nagoya Medical Center, Nagoya, Japan.
⁷ Kobe City Medical Center General Hospital, Hyogo, Japan.
⁸ NTT Medical Center Tokyo, Tokyo, Japan.
⁹ Hokkaido University, Sapporo, Japan.
¹⁰ Saitama Medical Center, Saitama Medical University, Kawagoe, Japan.
¹¹ Aomori Prefectural Central Hospital, Aomori, Japan.
¹² Kyoto Prefectural University of Medicine, Kyoto, Japan.
¹³ International University of Health and Welfare (IUHW), Mita Hospital, Tokyo, Japan.
¹⁴ Keio University School of Medicine, Tokyo, Japan.
¹⁵ University of Tsukuba, Tsukuba, Japan.
¹⁶ Akita University, Akita, Japan.
¹⁷ Nagasaki University, Nagasaki, Japan.
¹⁸ Kumamoto Medical Center, Kumamoto, Japan.
¹⁹ Jichi Medical University, Shimotsuke, Japan.
²⁰ Okayama University Hospital, Okayama, Japan.
²¹ Kindai University, Osaka, Japan.
²² Astellas Pharma, Inc., Tokyo, Japan.
²³ Astellas Pharma US, Inc., Northbrook, IL, USA.
²⁴ Tokyo Metropolitan Ohtsuka Hospital, Tokyo, Japan.

Abstract

Background: Until recently, no effective targeted therapies for FLT3-mutated (FLT3^mut+) relapsed/refractory (R/R) acute myeloid leukemia (AML) were available in Japan. The FLT3 inhibitor, gilteritinib, was approved in Japan for patients with FLT3^mut+ 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.

Keywords: Acute myeloid leukemia; FLT3 inhibitor; FLT3 mutations.

Publication types

Randomized Controlled Trial

MeSH terms

Aniline Compounds
Humans
Japan
Leukemia, Myeloid, Acute* / drug therapy
Leukemia, Myeloid, Acute* / genetics
Mutation
Pyrazines*
fms-Like Tyrosine Kinase 3 / genetics

Substances

Aniline Compounds
Pyrazines
gilteritinib
FLT3 protein, human
fms-Like Tyrosine Kinase 3