TY - JOUR
T1 - Allogeneic hematopoietic stem cell transplantation at the first remission for younger adults with FLT3-internal tandem duplication AML
T2 - The JALSG AML209-FLT3-SCT study
AU - Kawashima, Naomi
AU - Ishikawa, Yuichi
AU - Atsuta, Yoshiko
AU - Sawa, Masashi
AU - Ozawa, Yukiyasu
AU - Hayashi, Masaki
AU - Kohno, Akio
AU - Tomita, Akihiro
AU - Maeda, Tomoya
AU - Sakaida, Emiko
AU - Usuki, Kensuke
AU - Hagihara, Maki
AU - Kanamori, Heiwa
AU - Matsuoka, Hiroshi
AU - Kobayashi, Miki
AU - Asou, Norio
AU - Ohtake, Shigeki
AU - Matsumura, Itaru
AU - Miyazaki, Yasushi
AU - Naoe, Tomoki
AU - Kiyoi, Hitoshi
N1 - Funding Information:
HK received research funding from Chugai Pharmaceutical, Kyowa Hakko Kirin, Zenyaku Kogyo, Fujifilm, Astellas Pharma, Otsuka Pharmaceutical, Nippon Shinyaku, Eisai, Pfizer Japan, Takeda Pharmaceutical, Novartis Pharma, Sumitomo Dainippon Pharma, Sanofi, and Celgene, consulting fees from Astellas Pharma, Amgen Astellas BioPharma, and Daiichi Sankyo, and honoraria from Bristol‐Myers Squibb, Astellas Pharma, and Novartis Pharma. KU received research funding from MSD, Astellas Pharma, Abbvie, Alexion Pharma, Gilead, GlaxoSmithKline, Sanofi, Shire, Symbio Pharmaceuticals, and Janssen Pharmaceutical, and speakers bureau from Novartis Pharma, Ono Pharmaceutical, Takeda Pharmaceutical, Chugai Pharmaceutical, Nippon Shinyaku, Mochida Pharmaceutical, MSD, Celgene, Sumitomo Dainippon Pharma, and Pfizer Japan. NA received research funding from Chugai Pharmaceutical, Astellas Pharma, Sumitomo Dainippon Pharma, Asahi Kasei Pharma, Eisai, consulting fees from Nippon Shinyaku, SRL, and honoraria from Sumitomo Dainippon Pharma, Asahi Kasei Pharma, Novartis Pharma, Kyowa Hakko Kirin, and Nippon Shinyaku. IM received research funding from Chugai Pharmaceutical, Kyowa Hakko Kirin, Otsuka Pharmaceutical, Novartis Pharma, Sumitomo Dainippon Pharma, Bristol‐Myers Squibb, Astellas Pharma, and honoraria from Novartis Pharma and Bristol‐Myers Squibb. YM received research funding from Chugai Pharmaceutical, and honoraria from Nippon Shinyaku, Novartis Pharma, Sumitomo Dainippon Pharma, Kyowa Hakko Kirin, and Otsuka Pharma.
Funding Information:
This study was supported by a grant from the Practical Research for Innovative Cancer Control from the Japan Agency for Medical Research and Development, AMED to HK (19ck0106251). We would like to thank the clinicians and leaders of the 39 institutions who entered their patients into the JALSG AML209‐FLT3‐SCT study and provided the necessary data to make this study possible.
Publisher Copyright:
© 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.
PY - 2020/7/1
Y1 - 2020/7/1
N2 - In this phase II multicenter study (JALSG AML209-FLT3-SCT), we aimed to prospectively elucidate the role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) at first complete remission (CR1) for FLT3-internal tandem duplication (ITD)-positive AML. Newly diagnosed de novo AML patients with FLT3-ITD were enrolled at the achievement of CR1 and received allo-HSCT as soon as possible after the first consolidation therapy. Mutations of 57 genes in AML cells at diagnosis were also analyzed. Among 48 eligible patients with a median age of 38.5 (17-49) years, 36 (75%) received allo-HSCT at a median of 108 days after CR1. The median follow-up was 1726 days. The primary end-point, 3-year disease-free survival (DFS) based on an intent to treat analysis, was 43.8% (95% confidence interval [CI], 30%-57%), suggesting the efficacy of this treatment because the lower limit of the 95% CI exceeded the threshold response rate of 20%. The 3-year overall survival, post-transplant DFS, and non-relapse mortality rates were 54.2% (95% CI, 39%-67%), 58.3% (95% CI, 41%-72%), and 25.0% (95% CI, 12%-40%), respectively. The median ITD allelic ratio (AR) was 0.344 (0.006-4.099). Neither FLT3-ITD AR nor cooccurring genetic alterations was associated with a poor DFS. This prospective study indicated the efficacy and safety of allo-HSCT for FLT3-ITD AML patients in CR1. This study was registered at: www.umin.ac.jp/ctr/ as #UMIN000003433.
AB - In this phase II multicenter study (JALSG AML209-FLT3-SCT), we aimed to prospectively elucidate the role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) at first complete remission (CR1) for FLT3-internal tandem duplication (ITD)-positive AML. Newly diagnosed de novo AML patients with FLT3-ITD were enrolled at the achievement of CR1 and received allo-HSCT as soon as possible after the first consolidation therapy. Mutations of 57 genes in AML cells at diagnosis were also analyzed. Among 48 eligible patients with a median age of 38.5 (17-49) years, 36 (75%) received allo-HSCT at a median of 108 days after CR1. The median follow-up was 1726 days. The primary end-point, 3-year disease-free survival (DFS) based on an intent to treat analysis, was 43.8% (95% confidence interval [CI], 30%-57%), suggesting the efficacy of this treatment because the lower limit of the 95% CI exceeded the threshold response rate of 20%. The 3-year overall survival, post-transplant DFS, and non-relapse mortality rates were 54.2% (95% CI, 39%-67%), 58.3% (95% CI, 41%-72%), and 25.0% (95% CI, 12%-40%), respectively. The median ITD allelic ratio (AR) was 0.344 (0.006-4.099). Neither FLT3-ITD AR nor cooccurring genetic alterations was associated with a poor DFS. This prospective study indicated the efficacy and safety of allo-HSCT for FLT3-ITD AML patients in CR1. This study was registered at: www.umin.ac.jp/ctr/ as #UMIN000003433.
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U2 - 10.1111/cas.14448
DO - 10.1111/cas.14448
M3 - Article
C2 - 32391628
AN - SCOPUS:85085523069
VL - 111
SP - 2472
EP - 2481
JO - Cancer Science
JF - Cancer Science
SN - 1347-9032
IS - 7
ER -