PMID- 33152120
OWN - NLM
STAT- MEDLINE
DCOM- 20210426
LR  - 20210429
IS  - 1365-2141 (Electronic)
IS  - 0007-1048 (Print)
IS  - 0007-1048 (Linking)
VI  - 192
IP  - 1
DP  - 2021 Jan
TI  - Efficacy and safety of romiplostim in refractory aplastic anaemia: a Phase 
      II/III, multicentre, open-label study.
PG  - 190-199
LID - 10.1111/bjh.17190 [doi]
AB  - A previous dose-finding study has suggested that romiplostim is effective in 
      patients with refractory aplastic anaemia (AA) and 10 microg/kg once weekly was 
      recommended as a starting dose. In this Phase II/III, multicentre, open-label 
      study, romiplostim was administered subcutaneously at a fixed dose of 10 microg/kg 
      once weekly for 4 weeks (weeks 1-4) followed by weekly doses (5, 10, 15 and 
      20 microg/kg) titrated by platelet response for up to 52 weeks (weeks 5-52). A total 
      of 31 patients with AA who were refractory to immunosuppressive therapy (IST) and 
      thrombocytopenia (platelet count of </=30 x 10(9) /l) were enrolled. The primary 
      efficacy endpoint of the proportion of patients achieving any haematological 
      (platelet, neutrophil and erythrocyte) response at week 27 was 84% [95% 
      confidence interval (CI) 66-95%]. Trilineage response was 39% (95% CI 22-58%) at 
      week 53. The most common treatment-related adverse events (AEs) were headache and 
      muscle spasms (each 13%). All AEs were mild or moderate except for three patients 
      with Grade 3 hepatic AEs; no AEs necessitated romiplostim discontinuation. Two 
      patients developed cytogenetic abnormalities, of whom one returned to normal 
      karyotype at last follow-up. High-dose romiplostim is effective and well 
      tolerated in the treatment of patients with AA refractory to IST.
CI  - (c) 2020 The Authors. British Journal of Haematology published by British Society 
      for Haematology and John Wiley & Sons Ltd.
FAU - Jang, Jun Ho
AU  - Jang JH
AD  - Department of Hematology, Sungkyunkwan University Samsung Medical Center, Seoul, 
      Republic of Korea.
FAU - Tomiyama, Yoshiaki
AU  - Tomiyama Y
AD  - Department of Blood Transfusion, Osaka University Hospital, Osaka, Japan.
FAU - Miyazaki, Koji
AU  - Miyazaki K
AD  - Department of Transfusion and Cell Transplantation, Kitasato University School of 
      Medicine, Sagamihara, Japan.
FAU - Nagafuji, Koji
AU  - Nagafuji K
AUID- ORCID: 0000-0003-4795-121X
AD  - Department of Hematology, Kurume University Hospital, Kurume, Japan.
FAU - Usuki, Kensuke
AU  - Usuki K
AD  - Department of Hematology, NTT Medical Center Tokyo, Tokyo, Japan.
FAU - Uoshima, Nobuhiko
AU  - Uoshima N
AD  - Department of Hematology, Japanese Red Cross Kyoto Daini Hospital, Kyoto, Japan.
FAU - Fujisaki, Tomoaki
AU  - Fujisaki T
AD  - Department of Internal Medicine, Matsuyama Red Cross Hospital, Matsuyama, Japan.
FAU - Kosugi, Hiroshi
AU  - Kosugi H
AD  - Department of Hematology, Ogaki Municipal Hospital, Ogaki, Japan.
FAU - Matsumura, Itaru
AU  - Matsumura I
AD  - Department of Hematology and Rheumatology, Kindai University Faculty of Medicine, 
      Osaka, Japan.
FAU - Sasaki, Ko
AU  - Sasaki K
AD  - Department of Hematology and Oncology, Dokkyo Medical University, Tochigi, Japan.
FAU - Kizaki, Masahiro
AU  - Kizaki M
AD  - Department of Hematology, International Medical Center, Saitama Medical 
      University, Saitama, Japan.
FAU - Sawa, Masashi
AU  - Sawa M
AD  - Department of Hematology and Oncology, Anjo Kosei Hospital, Anjo, Japan.
FAU - Hidaka, Michihiro
AU  - Hidaka M
AD  - Department of Hematology, National Hospital Organization Kumamoto Medical Center, 
      Kumamoto, Japan.
FAU - Kobayashi, Naoki
AU  - Kobayashi N
AD  - Department of Hematology, Sapporo Hokuyu Hospital, Sapporo, Japan.
FAU - Ichikawa, Satoshi
AU  - Ichikawa S
AUID- ORCID: 0000-0003-3163-7197
AD  - Department of Hematology and Rheumatology, Tohoku University Hospital, Sendai, 
      Japan.
FAU - Yonemura, Yuji
AU  - Yonemura Y
AD  - Department of Transfusion Medicine and Cell Therapy, Kumamoto University 
      Hospital, Kumamoto, Japan.
FAU - Enokitani, Kouki
AU  - Enokitani K
AUID- ORCID: 0000-0002-8360-0102
AD  - Kyowa Kirin Co., Ltd., Tokyo, Japan.
FAU - Matsuda, Akira
AU  - Matsuda A
AD  - Department of Hemato-Oncology, International Medical Center, Saitama Medical 
      University, Saitama, Japan.
FAU - Ozawa, Keiya
AU  - Ozawa K
AD  - Division of Hematology, Jichi Medical University, Tochigi, Japan.
FAU - Mitani, Kinuko
AU  - Mitani K
AUID- ORCID: 0000-0001-9736-9469
AD  - Department of Hematology and Oncology, Dokkyo Medical University, Tochigi, Japan.
FAU - Lee, Jong Wook
AU  - Lee JW
AD  - Division of Hematology, Seoul St. Mary's Hospital, The Catholic University of 
      Korea, Seoul, Republic of Korea.
FAU - Nakao, Shinji
AU  - Nakao S
AD  - Division of Transfusion Medicine, Kanazawa University Hospital, Kanazawa, Japan.
LA  - eng
GR  - Kyowa Kirin Co., Ltd./
PT  - Clinical Trial, Phase II
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20201105
PL  - England
TA  - Br J Haematol
JT  - British journal of haematology
JID - 0372544
RN  - 0 (Receptors, Fc)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 9014-42-0 (Thrombopoietin)
RN  - GN5XU2DXKV (romiplostim)
SB  - IM
CIN - Br J Haematol. 2021 Jan;192(1):15-16. PMID: 33152102
EIN - Br J Haematol. 2021 May;193(3):682. PMID: 33914338
MH  - Adult
MH  - Aged
MH  - Anemia, Aplastic/blood/*drug therapy
MH  - Anemia, Refractory/blood/*drug therapy
MH  - Blood Cell Count
MH  - Female
MH  - Headache/chemically induced
MH  - Hematopoiesis/drug effects
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Receptors, Fc/administration & dosage/blood/*therapeutic use
MH  - Recombinant Fusion Proteins/administration & dosage/adverse 
      effects/blood/*therapeutic use
MH  - Spasm/chemically induced
MH  - Thrombopoietin/administration & dosage/adverse effects/blood/*therapeutic use
MH  - Treatment Outcome
MH  - Young Adult
PMC - PMC7821109
OTO - NOTNLM
OT  - aplastic anaemia
OT  - bone marrow failure
OT  - haematopoiesis
OT  - thrombopoietin
COIS- Yoshiaki Tomiyama honoraria from Novartis Pharma K.K., Chugai Pharmaceutical Co., 
      Ltd. and Kyowa Kirin Co., Ltd.; and advisory committee member for Novartis Pharma 
      K.K. Koji Miyazaki honoraria from Kyowa Kirin Co., Ltd., Chugai Pharmaceutical 
      Co., Ltd., Pfizer Japan, Inc., Novartis Pharma K.K., Novo Nordisk Pharma Ltd., KM 
      Biologics, Nihon Pharmaceutical Co., Ltd. and CSL Behring K.K.; and research 
      funding from Kyowa Kirin Co., Ltd., Chugai Pharmaceutical Co., Ltd., Pfizer Japan 
      Inc., Daiichi Sankyo Co., Ltd., Astellas Pharma Inc., Otsuka Pharmaceutical Co., 
      Ltd., Takeda Pharmaceutical Co., Ltd. and MSD K.K. Kensuke Usuki research funding 
      from Astellas Pharma Inc., Alexion Pharmaceuticals, AbbVie GK, Gilead, SymBio 
      Pharmaceuticals Ltd., Daiichi Sankyo Co., Ltd., Sumitomo Dainippon Pharma Co., 
      Ltd., Chugai Pharmaceutical Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Novartis 
      Pharma K.K., Bristol-Myers Squibb Company, Ono Pharmaceutical Co., Ltd., Janssen 
      Pharmaceutical K.K., Celgene Corporation, Takeda Pharmaceutical Co., Ltd., Nippon 
      Boehringer Ingelheim Co., Ltd., Mundipharma K.K., Astellas-Amgen-Biopharma KK, 
      Apellis Pharmaceuticals Inc, Nippon Shinyaku Co., Ltd., Kyowa Kirin Co., Ltd. and 
      Pfizer Japan Inc.; and speakers bureaus for Novartis Pharma K.K., Alexion 
      Pharmaceuticals, Eisai Co., Ltd., Ono Pharmaceutical Co., Ltd., Kyowa Kirin Co., 
      Ltd., MSD K.K., Otsuka Pharmaceutical Co., Ltd., SymBio Pharmaceuticals Ltd., 
      Celgene Corporation, Daiichi Sankyo Co., Ltd., Takeda Pharmaceutical Co., Ltd., 
      Nippon Shinyaku Co., Ltd., PharmaEssentia Corp., Bristol-Myers Squibb Company and 
      Yakult Honsha Co. Ltd. Hiroshi Kosugi honoraria from Chugai Pharmaceutical Co., 
      Ltd., Celgene Corporation, Novartis Pharma K.K., Bioverativ Japan, MSD K.K., 
      Takeda Pharmaceutical Co., Ltd., Janssen Pharmaceutical K.K., Japan Blood 
      Products Organization, Bristol-Myers Squibb Company and Ono Pharmaceutical Co., 
      Ltd. Itaru Matsumura research funding from Kyowa Kirin Co., Ltd. Masahiro Kizaki 
      research funding and speakers bureau from Bristol-Myers Squibb Company, Celgene 
      Corporation and Nippon Shinyaku Co., Ltd.; and speakers bureaus from 
      Bristol-Myers Squibb Company, Celgene Corporation, Nippon Shinyaku Co., Ltd. and 
      Novartis Pharma K.K. Masashi Sawa honoraria from Celgene Corporation, Takeda 
      Pharmaceutical Co., Ltd., Bristol-Myers Squibb Company, Novartis International 
      AG, Chugai Pharmaceutical Co., Ltd. and Mundipharma K.K. Michihiro Hidaka 
      research funding from Chugai Pharmaceutical Co., Ltd. Yuji Yonemura honoraria 
      Alexion Pharmaceuticals, Novartis Pharma K.K., Chugai Pharmaceutical Co., Ltd., 
      Kyowa Kirin Co., Ltd. and Japan Blood Products Organization; and research funding 
      from Alexion Pharmaceuticals. Kouki Enokitani employed by Kyowa Kirin Co., Ltd. 
      A.M. honoraria from GlaxoSmithKline K.K., Novartis Pharma K.K., Chugai 
      Pharmaceutical Co., Ltd., Kyowa Kirin Co., Ltd., Sumitomo Dainippon Pharma Co., 
      Ltd., Nippon Shinyaku Co., Ltd., Celgene Corporation, Alexion Pharmaceuticals, 
      Sanofi K.K., Beckman Coulter, Inc., Siemens Healthineers and Shire Japan; 
      research funding from Chugai Pharmaceutical Co., Ltd., Sumitomo Dainippon Pharma 
      Co., Ltd., Novartis Pharma K.K., Astellas Pharma Inc., Asahi Kasei Pharma 
      Corporation, Eisai Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Nippon Boehringer 
      Ingelheim Co., Ltd., MSD K.K., Daiichi Sankyo Co., Ltd., AbbVie GK, HUYA 
      Bioscience International, Kyowa Kirin Co., Ltd., Taiho Pharmaceutical Co., Ltd., 
      Nippon Shinyaku Co., Ltd., Daiichi Sankyo Co., Ltd., Sanofi K.K., Pfizer Japan, 
      Inc., Teijin Pharma, Ltd. and Takeda Pharmaceutical Co., Ltd.; and speakers 
      bureaus for Kyowa Kirin Co., Ltd., Bristol-Myers Squibb Company and Celgene 
      Corporation. Kinuko Mitani consulting fees Kyowa Kirin Co., Ltd.; on speakers 
      bureaus for Kyowa Kirin Co., Ltd., Bristol-Myers Squibb Company and Celgene 
      Corporation; and research funding from Kyowa Kirin Co., Ltd., Chugai 
      Pharmaceutical Co., Ltd., Astellas Pharma Inc., Sumitomo Dainippon Pharma Co., 
      Ltd., Taiho Pharmaceutical Co., Ltd., Nippon Shinyaku Co., Ltd., Daiichi Sankyo 
      Co., Ltd., Sanofi K.K., Pfizer Japan Inc., Teijin Pharma Ltd. and Takeda 
      Pharmaceutical Co., Ltd. Jong Wook Lee honoraria, consulting fees and research 
      support (to Seoul St. Mary's Hospital) from Alexion Pharmaceuticals; and advisory 
      board member for Alexion Pharmaceuticals. Shinji Nakao honoraria from Novartis 
      Pharma K.K., Kyowa Kirin Co., Ltd. and Alexion Pharmaceuticals. Jun Ho Jang, Koji 
      Nagafuji, Nobuhiko Uoshima, Tomoaki Fujisaki, Ko Sasaki, Naoki Kobayashi, Satoshi 
      Ichikawa and Keiya Ozawa have no competing interests.
EDAT- 2020/11/06 06:00
MHDA- 2021/04/27 06:00
PMCR- 2021/01/22
CRDT- 2020/11/05 17:14
PHST- 2020/06/07 00:00 [received]
PHST- 2020/08/17 00:00 [accepted]
PHST- 2020/11/06 06:00 [pubmed]
PHST- 2021/04/27 06:00 [medline]
PHST- 2020/11/05 17:14 [entrez]
PHST- 2021/01/22 00:00 [pmc-release]
AID - BJH17190 [pii]
AID - 10.1111/bjh.17190 [doi]
PST - ppublish
SO  - Br J Haematol. 2021 Jan;192(1):190-199. doi: 10.1111/bjh.17190. Epub 2020 Nov 5.