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