阿伐曲泊帕作为对艾曲泊帕不耐受或无反应的重型再生障碍性贫血患者的替代疗法。
Avatrombopag as alternative therapy for severe aplastic anemia patients who are intolerant or unresponsive to eltrombopag.
作者信息
Zhang Ting, Yu Qingling, Chen Xiaoyu, Yang Hui, Gong Yuemin, Zhang Yawen, Liu Xiaoqing, Yang Zhinan, Fang Yu, Yan Xue, Zhou Xuan, Shi Jinning, He Guangsheng
机构信息
Department of Hematology, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, China.
Department of Hematology, Affiliated Jianhu Hospital of Nantong University Xinglin College, Yancheng, China.
出版信息
Front Immunol. 2024 Jul 24;15:1393829. doi: 10.3389/fimmu.2024.1393829. eCollection 2024.
INTRODUCTION
Eltrombopag (EPAG), a thrombopoietin receptor agonist, was approved for the treatment of severe aplastic anemia (SAA) combined with immunosuppressive therapy (IST). However, EPAG contains a typical biphenyl structure, which causes liver function damage.
METHODS
Twenty patients with SAA who were intolerant or refractory to EPAG were enrolled in a multicenter prospective registry of the Chinese Eastern Collaboration Group of Anemia (ChiCTR2100045895) from October 2020 to June 2023.
RESULTS
Eight patients who were ineffective to EPAG, six with kidney impairment, and nine with abnormal liver function (two with concomitant liver and kidney impairment) were converted to avatrombopag (AVA) therapy with the median duration of AVA treatment was 6 (3-24) months. 17 cases (85%) achieved trilineage hematological response (HR): complete remission (CR) in 3 cases (15%), good partial remission (GPR) in 4 cases (20%), partial remission (PR) in 10 cases (50%), and no response (NR) in 3 cases (15%). The median time to response was 1.7 (0.5-6.9) months, with 16 cases (94%) achieving response within six months and 17 cases (100%) within 12 months. 9 cases (50%) achieved transfusion independence. AVA converted treatment was associated with higher neutrophil counts (0.8×10/L vs 2.2×10/L, p=0.0003), platelet counts (11×10/L vs 39×10/L, p=0.0008), hemoglobin count (59g/L vs 98g/L, p=0.0002), red cell count (1.06×10/L vs 2.97×10/L, p=0.001), and absolute reticulocyte count (31.99 ×10/L vs 67.05×10/L p=0.0004) were all significantly elevated compared with the pre-treatment level. After the conversion to AVA therapy, liver and kidney function indexes were maintained within the normal range, no AVA related grade 2 or higher adverse events occurred, and no thrombotic events occurred.
CONCLUSION
The conversion to AVA was an optimal choice for patients with SAA who were EPAG intolerant or refractory.
CLINICAL TRIAL REGISTRATION
http://www.chictr.org.cn/showproj.html?proj=125480, identifier ChiCTR2100045895.
引言
艾曲泊帕（EPAG）是一种血小板生成素受体激动剂，已被批准用于联合免疫抑制疗法（IST）治疗重型再生障碍性贫血（SAA）。然而，EPAG含有典型的联苯结构，会导致肝功能损害。
方法
2020年10月至2023年6月，20例对EPAG不耐受或难治的SAA患者被纳入中国东部贫血协作组多中心前瞻性注册研究（ChiCTR2100045895）。
结果
8例对EPAG无效、6例有肾功能损害、9例有肝功能异常（2例同时有肝肾功能损害）的患者转为阿伐曲泊帕（AVA）治疗，AVA治疗的中位持续时间为6（3 - 24）个月。17例（85%）达到三系血液学缓解（HR）：3例（15%）完全缓解（CR），4例（20%）良好部分缓解（GPR），10例（50%）部分缓解（PR），3例（15%）无缓解（NR）。中位缓解时间为1.7（0.5 - 6.9）个月，16例（94%）在6个月内达到缓解，17例（100%）在12个月内达到缓解。9例（50%）实现了输血独立。与治疗前水平相比，AVA转换治疗后中性粒细胞计数（0.8×10⁹/L对2.2×10⁹/L，p = 0.0003）、血小板计数（11×10⁹/L对39×10⁹/L，p = 0.0008）、血红蛋白计数（59g/L对98g/L，p = 0.0002）、红细胞计数（1.06×10¹²/L对2.97×10¹²/L，p = 0.001）和绝对网织红细胞计数（31.99×10⁹/L对67.05×10⁹/L，p = 0.0004）均显著升高。转换为AVA治疗后，肝肾功能指标维持在正常范围内，未发生与AVA相关的2级或更高等级不良事件，也未发生血栓事件。
结论
对于EPAG不耐受或难治的SAA患者，转换为AVA是最佳选择。
临床试验注册
http://www.chictr.org.cn/showproj.html?proj=125480，标识符ChiCTR2100045895。
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