Department of Haematology, Royal Manchester Children's Hospital, Faculty of Medical & Human Sciences, University of Manchester, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
Department of Pediatrics, Division of Hematology, Weill Cornell Medicine, New York, NY.
Blood Adv. 2023 Feb 14;7(3):396-405. doi: 10.1182/bloodadvances.2021006014.
Romiplostim is a thrombopoietin (TPO) receptor agonist approved for children and adults with immune thrombocytopenia (ITP) for ≥6 months, recommended as second-line treatment. This phase 3b, single-arm, multicenter study investigated long-term efficacy and safety of romiplostim in children ≥1 to <18 years old with ≥6 months' ITP duration and platelet counts ≤30 × 109/L. Children received weekly subcutaneous romiplostim (1 μg/kg titrated to 10 μg/kg) to maintain platelets within 50 to 200 × 109/L. A subset underwent bone marrow examinations. The primary end point was percentage of time with platelet response during the first 6 months' treatment (counts ≥50 × 109/L without rescue medication within the preceding 4 weeks). Overall, 203 patients (median age, 10.0 years) received ≥1 dose of romiplostim, median treatment duration was ∼3 years, and median average weekly dose was 6.9 μg/kg. Ninety-five (46.8%) discontinued (lack of efficacy, n = 43 [21.2%]). Platelet responses were achieved a median (interquartile range) of 50.0% (16.7%-83.3%) of the time during the first 6 months, increasing to 78.2% (26.7%-90.4%) during the overall 36-month treatment period. Eleven patients (5.4%) achieved sustained responses (consecutive counts ≥50 × 109/L without ITP medications for ≥24 weeks). Treatment-related adverse events (AEs) occurred in 56 patients (27.6%), with 8 (3.9%) experiencing serious treatment-related AEs; all of these led to discontinuation, including 4 cases of neutralizing antibodies (romiplostim, n = 3; TPO, n = 1). Bleeding occurred in 141 patients (69.5%), decreasing over time; grade ≥3 bleeding events occurred in 20 (9.9%). At year 2, eight of 63 evaluable patients (12.7%) had grade 2 reticulin. Long-term romiplostim resulted in sustained on-treatment platelet responses with an overall safety profile consistent with previous studies. This trial was registered at www.clinicaltrials.gov as #NCT02279173.
罗米司亭是一种血小板生成素（TPO）受体激动剂，已获批用于免疫性血小板减少症（ITP）持续时间≥6 个月的儿童和成人患者，推荐作为二线治疗药物。这项 3b 期、单臂、多中心研究调查了罗米司亭在 ITP 持续时间≥6 个月且血小板计数≤30×109/L 的≥1 至<18 岁儿童患者中的长期疗效和安全性。儿童患者每周接受皮下注射罗米司亭（1μg/kg 滴定至 10μg/kg），以将血小板维持在 50 至 200×109/L 之间。一部分患者进行了骨髓检查。主要终点是治疗的前 6 个月内血小板反应的时间百分比（在过去 4 周内无抢救药物的情况下计数≥50×109/L）。总体而言，203 例患者（中位年龄 10.0 岁）接受了≥1 剂罗米司亭治疗，中位治疗持续时间约为 3 年，平均每周剂量为 6.9μg/kg。95 例（46.8%）停药（无效，n=43[21.2%]）。在第 1 个 6 个月期间，血小板反应的中位数（四分位距）为 50.0%（16.7%-83.3%），在整个 36 个月的治疗期间增加到 78.2%（26.7%-90.4%）。11 例（5.4%）患者获得持续反应（连续计数≥50×109/L，无 ITP 药物治疗≥24 周）。56 例（27.6%）患者发生与治疗相关的不良事件（AE），8 例（3.9%）患者发生严重的治疗相关 AE；所有这些都导致停药，包括 4 例中和抗体（罗米司亭，n=3；TPO，n=1）。141 例（69.5%）患者发生出血，随时间减少；20 例（9.9%）患者发生≥3 级出血事件。在第 2 年，63 例可评估患者中有 8 例（12.7%）出现 2 级网状纤维。长期罗米司亭治疗可导致持续的血小板反应，整体安全性与既往研究一致。该试验在 www.clinicaltrials.gov 注册，编号为 #NCT02279173。
