Hematologic recovery induced by eltrombopag in Japanese patients with aplastic anemia refractory or intolerant to immunosuppressive therapy

  • Hirohito YamazakiEmail author
  • Kensuke Ohta
  • Hiroatsu Iida
  • Kazunori Imada
  • Naoshi Obara
  • Yukihiro Tokumine
  • Yoshiaki Tomiyama
  • Kensuke Usuki
  • Kenji Imajo
  • Koichi Miyamura
  • Osamu Sasaki
  • Zhang Fanghong
  • Toshihiro Hattori
  • Takeshi Tajima
  • Akira Matsuda
  • Shinji Nakao
Original Article


Eltrombopag, an oral thrombopoietin-receptor agonist, stimulates hematopoiesis in patients with acquired aplastic anemia (AA) and has higher exposure in patients of East Asian origin. We evaluated the pharmacokinetics, efficacy, and safety of eltrombopag in Japanese patients with AA refractory or intolerant to immunosuppressive therapy (IST). Twenty-one patients (15 with non-severe AA, six with severe AA) with platelet counts < 30,000/µL received eltrombopag in a dose-escalation fashion (25, 50, 75, or 100 mg once daily) depending on individual platelet responses; the responders continued eltrombopag treatment beyond 6 months. The primary endpoint was hematologic response at 6 months, defined as improvements in blood counts or transfusion requirements. Ten (48%) patients achieved hematologic responses in at least one lineage at 6 months. Six patients achieved tri- and/or bi-lineage responses with continuation of eltrombopag treatment, with two patients no longer requiring eltrombopag treatment. The most common adverse events were nasopharyngitis and abnormal hepatic function, with the majority being grade 1 or 2. Cytogenetic abnormalities were observed in three patients; however, no progression to myelodysplastic syndrome/other malignancy was observed. Eltrombopag can safely restore multi-lineage hematopoiesis in Japanese patients with AA refractory or intolerant to IST.

Clinical Trial registration NCT02148133.


Eltrombopag Japanese patients Aplastic anemia Inter-ethnic difference 



We thank Mittal Makhija and Anamika Gulati (Novartis Healthcare Private Limited, Hyderabad, India) for providing medical writing and editorial support to draft the manuscript.


The study was funded by GlaxoSmithKline; however, as of March 2, 2015, eltrombopag is an asset of Novartis Pharma AG.

Compliance with ethical standards

Conflict of interest

HY has received grant/personal fees/non-financial support from Novartis. KO has received personal fees from Takeda, Celgene, Janssen, Bristol-Meyers Squibb, Ono, and Novartis. KI have received personal fees from Novartis, Bristol-Meyers Squibb, Takeda, Celgene, Nippon Shinyaku, MSD, Chugai, and Sumitomo Dainippon. YT received personal fees Novartis, Kyowa Hakko Kirin, and Chugai and provided advisory role to Novartis and Sysmex. HI, KM, and NO have declared no conflict of interest. KU has received grants from Astellas, AbbVie, Alexion, Gilead Sciences, SimBio, Daiichi-Sankyo, Sumitomo Dainippon, and personal fees from Novartis. TH, TT, and ZF are employees of Novartis. AM received personal fees from GlaxoSmithKline and Novartis Pharma during the conduct of the study, grants, and personal fees from Chugai, Kyowa Hakko Kirin, Sumitomo Dainippon, Nippon Shinyaku, GlaxoSmithKline, Novartis, Celgene, Alexion, Sanofi and Beckman Coulter, Shire Japan KK, Astellas, Asahi Kasei, Eisai, Otsuka, Boehringer Ingelheim, MSD, Daiichi-Sankyo, Abbvie, and HUYA Bioscience. SN has received personal fees from Novartis and Alexion.


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Copyright information

© Japanese Society of Hematology 2019

Authors and Affiliations

  • Hirohito Yamazaki
    • 1
    Email author
  • Kensuke Ohta
    • 2
  • Hiroatsu Iida
    • 3
  • Kazunori Imada
    • 4
  • Naoshi Obara
    • 5
  • Yukihiro Tokumine
    • 6
  • Yoshiaki Tomiyama
    • 7
  • Kensuke Usuki
    • 8
  • Kenji Imajo
    • 9
  • Koichi Miyamura
    • 10
  • Osamu Sasaki
    • 11
  • Zhang Fanghong
    • 12
  • Toshihiro Hattori
    • 12
  • Takeshi Tajima
    • 12
  • Akira Matsuda
    • 13
  • Shinji Nakao
    • 14
  1. 1.Division of Transfusion MedicineKanazawa University HospitalKanazawaJapan
  2. 2.Hematology Ohta ClinicOsakaJapan
  3. 3.National Hospital Organization Nagoya Medical CenterNagoyaJapan
  4. 4.Japanese Red Cross Osaka HospitalOsakaJapan
  5. 5.University of TsukubaTsukubaJapan
  6. 6.Itami City HospitalItamiJapan
  7. 7.Osaka University HospitalOsakaJapan
  8. 8.NTT Medical Center TokyoTokyoJapan
  9. 9.Okayama City HospitalOkayamaJapan
  10. 10.Japanese Red Cross Nagoya Daiichi HospitalNagoyaJapan
  11. 11.Miyagi Cancer CenterNatoriJapan
  12. 12.Novartis Pharma K.KTokyoJapan
  13. 13.International Medical CenterSaitama Medical UniversitySaitamaJapan
  14. 14.Kanazawa University Institute of Medical Pharmaceutical and Health SciencesKanazawaJapan

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