TY - JOUR
T1 - Dasatinib-based 2-step induction for adults with Philadelphia chromosome-positive acute lymphoblastic leukemia
AU - Sugiura, Isamu
AU - Doki, Noriko
AU - Hata, Tomoko
AU - Cho, Ryuko
AU - Ito, Toshiro
AU - Suehiro, Youko
AU - Tanaka, Masatsugu
AU - Kako, Shinichi
AU - Matsuda, Mitsuhiro
AU - Yokoyama, Hisayuki
AU - Ishikawa, Yuichi
AU - Taniguchi, Yasuhiro
AU - Hagihara, Maki
AU - Ozawa, Yukiyasu
AU - Ueda, Yasunori
AU - Hirano, Daiki
AU - Sakura, Toru
AU - Tsuji, Masaaki
AU - Kamae, Tsuyoshi
AU - Fujita, Hiroyuki
AU - Hiramoto, Nobuhiro
AU - Onoda, Masahiro
AU - Fujisawa, Shin
AU - Hatta, Yoshihiro
AU - Dobashi, Nobuaki
AU - Nishiwaki, Satoshi
AU - Atsuta, Yoshiko
AU - Kobayashi, Yukio
AU - Hayakawa, Fumihiko
AU - Ohtake, Shigeki
AU - Naoe, Tomoki
AU - Miyazaki, Yasushi
N1 - Funding Information:
for Otsuka Pharmaceutical and Sanofi. S.F. has received research funding from Astellas Pharma and Pfizer Japan and honoraria from Bristol-Myers Squibb, Novartis Pharma, and Pfizer Japan. Y.H. has received honoraria from Bristol-Myers Squibb and Novartis Pharma. N. Dobashi has received research funding from AbbVie, Astellas Pharma, Chugai Pharmaceutical, Daiichi Sankyo, Eisai, Kyowa Kirin, Otsuka Pharmaceutical, PfizerJapan,andZenyaku Kogyo. Y.A.hasreceivedhonorariafromAstel-las Pharma, Mochida Pharmaceutical, and Meiji Seika Pharma. Y.K. has received research funding from Pfizer Japan, Nippon-Shinyaku, SymBio, andAmgen.F.H.hasreceivedresearchfundingfromChugaiPharmaceu-tical and Daiichi Sankyo Foundation of Life Science. T.N. has received research funding from Astellas Pharma, Daiichi Sankyo, and FUJIFILM and honoraria from Astellas Pharma, Nippon Shinyaku, Bristol-Myers Squibb, Sysmex, Pfizer Japan, Otsuka Pharmaceutical, and FUJIFILM. Y.M. has received research funding from Sumitomo-Dainippon and honoraria from Novartis Pharma, Celgene, Sumitomo-Dainippon, Chugai Pharmaceutical, Otsuka Pharmaceutical, Astellas Pharma, Kyowa Kirin, Amgen, Pfizer Japan, Nippon Shinyaku, Janssen Pharma, Bristol-Myers Squibb, Takeda Pharmaceutical, and Daiichi Sankyo. The remaining authors declare no competing financial interests.
Funding Information:
Conflict-of-interest disclosure: I.S. has received honoraria from Takeda Pharmaceutical, Novartis Pharma, Bristol-Myers Squibb, and PfizerJapan.Y.S.hasreceivedresearchfundingfromChugaiPharmaceu-tical, Novartis Pharma, Kyowa Kirin, Bayer, Eisai, Ono Pharma, Otsuka Pharmaceutical, Pfizer Japan, Amgen BioPharma, Celgene, and Takeda Pharmaceutical. S.K. has received honoraria from Bristol-Myers Squibb. H.Y. has received research funding from Astellas Pharma and honoraria fromAstellasPharma,AbbVie,TakedaPharmaceutical,JanssenPharma, Celgene,Bristol-MyersSquibb,andDaiichiSankyo.Y.I.hasreceivedhon-oraria from AbbVie, Astellas Pharma, Celgene, Chugai Pharmaceutical, FUJIFILM, Kyowa Kirin, and Novartis Pharma. Y.T. has received research fundingfromEisai.Y.O.hasreceivedhonorariafromPfizerJapan,Astellas Pharma,NovartisPharma,andKyowaKirin.Y.U.hasactedasaconsultant
Funding Information:
This study was supported by the following grants: a research program of the Project for Development of Innovative Research on Cancer Therapeutics, Ministry of Education, Culture, Sports, Science and Technology of Japan under grant JP15cm0106055 (2013-2015); the National Cancer Center Research and Development Fund (23-A-23 and 26-A-24); and the Japan Agency for Medical Research and Development under grants JP16ck0106129 and JP19ck0106331.
Publisher Copyright:
© 2022 American Society of Hematology. All rights reserved.
PY - 2022/1/25
Y1 - 2022/1/25
N2 - The standard treatment for adults with Philadelphia chromosome-positive (Ph1) acute lymphoblastic leukemia (ALL) in Japan is imatinib-based chemotherapy followed by allogeneic hematopoietic stem cell transplantation (HSCT). However, _40% of patients cannot undergo HSCT in their first complete remission (CR1) because of chemotherapy-related toxicities or relapse before HSCT or older age. In this study, we evaluated dasatinib-based 2-step induction with the primary end point of 3-year event-free survival (EFS). The first induction (IND1)was dasatinib plus prednisolone to achieve CR, and IND2 was dasatinib plus intensive chemotherapy to achieve minimal residual disease (MRD) negativity. For patients who achieved CR and had an appropriate donor, HSCT during a consolidation phase later than the first consolidation, which included high-dose methotrexate, was recommended. Patients with pretransplantation MRD positivity were assigned to receive prophylactic dasatinib after HSCT. All 78 eligible patients achieved CR or incomplete CR after IND1, and 52.6% achieved MRD negativity after IND2. Nonrelapse mortality (NRM) was not reported. T315Imutationwas detected in all 4 hematological relapses before HSCT. Fifty-eight patients (74.4%) underwent HSCT in CR1, and 44 (75.9%) had negative pretransplantation MRD. At a median follow-up of 4.0 years, 3-year EFS and overall survival were 66.2% (95% confidence interval [CI], 54.4-75.5) and 80.5% (95% CI, 69.7-87.7), respectively. The cumulative incidence of relapse and NRM at 3 years from enrollment were 26.1% and 7.8%, respectively. Dasatinib-based 2-step induction was demonstrated to improve 3-year EFS in Ph1 ALL. This study was registered in the UMIN Clinical Trial Registry as #UMIN000012173.
AB - The standard treatment for adults with Philadelphia chromosome-positive (Ph1) acute lymphoblastic leukemia (ALL) in Japan is imatinib-based chemotherapy followed by allogeneic hematopoietic stem cell transplantation (HSCT). However, _40% of patients cannot undergo HSCT in their first complete remission (CR1) because of chemotherapy-related toxicities or relapse before HSCT or older age. In this study, we evaluated dasatinib-based 2-step induction with the primary end point of 3-year event-free survival (EFS). The first induction (IND1)was dasatinib plus prednisolone to achieve CR, and IND2 was dasatinib plus intensive chemotherapy to achieve minimal residual disease (MRD) negativity. For patients who achieved CR and had an appropriate donor, HSCT during a consolidation phase later than the first consolidation, which included high-dose methotrexate, was recommended. Patients with pretransplantation MRD positivity were assigned to receive prophylactic dasatinib after HSCT. All 78 eligible patients achieved CR or incomplete CR after IND1, and 52.6% achieved MRD negativity after IND2. Nonrelapse mortality (NRM) was not reported. T315Imutationwas detected in all 4 hematological relapses before HSCT. Fifty-eight patients (74.4%) underwent HSCT in CR1, and 44 (75.9%) had negative pretransplantation MRD. At a median follow-up of 4.0 years, 3-year EFS and overall survival were 66.2% (95% confidence interval [CI], 54.4-75.5) and 80.5% (95% CI, 69.7-87.7), respectively. The cumulative incidence of relapse and NRM at 3 years from enrollment were 26.1% and 7.8%, respectively. Dasatinib-based 2-step induction was demonstrated to improve 3-year EFS in Ph1 ALL. This study was registered in the UMIN Clinical Trial Registry as #UMIN000012173.
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U2 - 10.1182/bloodadvances.2021004607
DO - 10.1182/bloodadvances.2021004607
M3 - Article
C2 - 34516628
AN - SCOPUS:85123534167
SN - 2473-9529
VL - 6
SP - 624
EP - 636
JO - Blood advances
JF - Blood advances
IS - 2
ER -