Jang Jun Ho, Mitani Kinuko, Tomiyama Yoshiaki, Miyazaki Koji, Nagafuji Koji, Usuki Kensuke, Uoshima Nobuhiko, Fujisaki Tomoaki, Kosugi Hiroshi, Matsumura Itaru, Sasaki Ko, Kizaki Masahiro, Sawa Masashi, Hidaka Michihiro, Kobayashi Naoki, Ichikawa Satoshi, Yonemura Yuji, Murotani Kenta, Shimizu Mami, Matsuda Akira, Ozawa Keiya, Nakao Shinji, Lee Jong Wook
Department of Hematology, Sungkyunkwan University Samsung Medical Center, Seoul, Republic of Korea.
Department of Hematology and Oncology, Dokkyo Medical University, Tochigi, Japan.
Ann Hematol. 2025 Jul 1. doi: 10.1007/s00277-025-06337-7.
The thrombopoietin receptor agonist (TPO-RA) romiplostim has been shown to be efficacious in the treatment of aplastic anemia (AA) refractory to immunosuppressive therapy. However, there are few reports on predictors of TPO-RA efficacy. We analyzed patient clinical and baseline laboratory data from two clinical trials that enrolled patients with refractory AA, a phase 2 dose-finding study (NCT02094417) and a phase 2/3 study (NCT02773290), to determine predictors of romiplostim efficacy. Data from 66 patients (35 from the phase 2 dose-finding study and 31 from the phase 2/3 study), median age 47.0 (range 20-78) years, were analyzed. Of these, 51.5% (34/66) had non-severe AA, 86.4% (57/66) had received prior therapy with anti-thymocyte globulin plus cyclosporine, and 80.3% (53/66) were transfusion-dependent. At 27 weeks, no patients achieved a complete response, 57.4% (35/61) achieved a partial response, 49.0% (24/49) became red blood cell transfusion-independent, and 56.8% (21/37) became platelet transfusion-independent. Univariate logistic regression analysis identified duration from diagnosis (P = 0.040), baseline reticulocyte count (P < 0.001), and platelet count (P < 0.001) as predictors of response to romiplostim at 27 weeks. Receiver operating characteristic curve analysis identified a cutoff value of 30.77 × 10/L at baseline as the threshold reticulocyte count to predict response to romiplostim in patients with refractory AA (sensitivity: 82.9%, specificity: 73.1%). Of note, the initial dose included in this analysis was lower than that used in real-world clinical practice, as data from the phase 2 dose-finding study were used. This study identified factors predicting response to romiplostim at 27 weeks.Trial registration: ClinicalTrials.gov NCT02094417 and NCT02773290.
血小板生成素受体激动剂（TPO-RA）罗米司亭已被证明在治疗对免疫抑制疗法难治的再生障碍性贫血（AA）中有效。然而，关于TPO-RA疗效预测因素的报道很少。我们分析了两项临床试验中患者的临床和基线实验室数据，这两项试验纳入了难治性AA患者，一项2期剂量探索研究（NCT02094417）和一项2/3期研究（NCT02773290），以确定罗米司亭疗效的预测因素。分析了66例患者的数据（35例来自2期剂量探索研究，31例来自2/3期研究），中位年龄47.0岁（范围20 - 78岁）。其中，51.5%（34/66）患有非重度AA，86.4%（57/66）曾接受过抗胸腺细胞球蛋白加环孢素的治疗，80.3%（53/66）依赖输血。在27周时，无患者达到完全缓解，57.4%（35/61）达到部分缓解，49.0%（24/49）不再依赖红细胞输血，56.8%（21/37）不再依赖血小板输血。单因素逻辑回归分析确定诊断后的病程（P = 0.040）、基线网织红细胞计数（P < 0.001）和血小板计数（P < 0.001）为27周时对罗米司亭反应的预测因素。受试者工作特征曲线分析确定基线时30.77×10⁹/L的截断值为预测难治性AA患者对罗米司亭反应的网织红细胞计数阈值（敏感性：82.9%，特异性：73.1%）。值得注意的是，由于使用了2期剂量探索研究的数据，本分析中包含的初始剂量低于实际临床实践中使用的剂量。本研究确定了27周时预测对罗米司亭反应的因素。试验注册：ClinicalTrials.gov NCT02094417和NCT02773290。
