Hetrombopag Added to Immunosuppressive Therapy in First-Line Treatment of Severe Aplastic Anemia: A Randomized, Double-Blind, Placebo-Controlled Phase 3 Trial

作者：Fengkui Zhang, Xin Zhao, Hong Chang, Bing Han, Sujun Gao, Miao Miao, Jianda Hu, Lingyu Lin, Xinjian Liu, Lina Zhang, Cheng‐Hao Jin, Yingmei Li, Shengyun Lin, Jinsong Jia, Yi Wang, Chunkang Chang, Zheng Ge, Guangsheng He, Ruixiang Xia, Xiangjun Fu, Yuhua Li, Hong Liu, Kai Sun, Shunqing Wang, Linghui Xia, Weihua Zhang, Runzi Li, Junye Xiong, Wanyi Zhai · 发表于：Blood · 年份：2024 · DOI：10.1182/blood-2024-206377 · 被引用次数：4 · 研究领域：Hematopoietic Stem Cell Transplantation、Platelet Disorders and Treatments、Blood groups and transfusion

Introduction: Immunosuppressive therapy (IST) combined with the thrombopoietin receptor agonist (TPO-RA) is the first-line recommendation for patients with severe aplastic anemia (SAA) who are not eligible for hematopoietic stem cell transplantation (HSCT). Hetrombopag, a novel small molecule TPO-RA, has demonstrated promising efficacy in IST-refractory SAA in our previous single-arm phase 2 study (NCT03557099). To further evaluate the efficacy and safety of hetrombopag in combination with standard IST as first-line treatment for untreated SAA patients, we conducted this randomized, double-blind, placebo-controlled phase 3 study (NCT03825744) and reported the results. Methods: Eligible patients aged 15-75 years with untreated SAA according to the Camitta criteria and ineligible for HSCT were enrolled. Patients were randomly assigned in a 2:1 ratio to receive either hetrombopag plus IST (antithymocyte globulin [ATG] and cyclosporine [CsA]) or placebo plus IST. Randomization was stratified based on the source of ATG (rabbit or pig-derived). Hetrombopag or placebo was administered orally on an empty stomach at a daily dose of 15 mg for 6 months. ATG was administered intravenously for 5 consecutive days, and CsA was given orally for 6 months. The primary endpoint was hematologic complete response (CR) rate at 6 months. Results: A total of 240 patients were randomized, with 160 patients in the hetrombopag group and 80 in the placebo group. At 6 months, the CR rate was 28.1% (95% C...