Steroid-refractory acute graft-versus-host disease (SR-aGVHD) following hematopoietic cell transplantation (HSCT) is associated with poor clinical outcomes. Currently, there are no safe and effective therapies approved for use in the pediatric population under the age of 12 years. Accordingly, there is an urgent need for new treatments that are safe, well tolerated, and effective in managing this debilitating and potentially fatal complication of HSCT. In early phase clinical trials, mesenchymal stromal cells (MSCs) have demonstrated efficacy in the treatment of acute GVHD (aGVHD) in pediatric patients. We now report the results of a phase 3, prospective, single-arm, multicenter study (NCT02336230) in 54 children with primary SR-aGVHD who were naive to other immunosuppressant therapies for aGVHD treated with MSC product (remestemcel-L) dosed at 2 × 106 cells/kg twice weekly for 4 weeks. Remestemcel-L therapy significantly improved day 28 overall response rate (OR) compared with the prespecified control OR value of 45% (70.4% versus 45%, P = .0003). The statistically significant OR (70.4%) was sustained through day 100, including an increase in complete response from 29.6% at day 28 to 44.4% at day 100. Overall survival was 74.1% at day 100 and 68.5% at day 180. Overall response in all participants at day 28 was highly predictive of improved survival through 180 days, and survival was significantly greater in day 28 responders compared with nonresponders through day 100 (86.8% versus 47.1% for responders and nonresponders, respectively, P = .0001) and through day 180 (78.9% versus 43.8%, P = .003). Remestemcel-L was well tolerated with no identified infusion-related toxicities or other safety concerns. This study provides robust, prospective evidence of the safety, tolerability, and efficacy of remestemcel-L as first-line therapy after initial steroid failure in pediatric SR-aGVHD.

中文翻译：

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Remestemcel-L、体外培养扩增的成人间充质基质细胞用于治疗急性移植物抗宿主病类固醇治疗无效的儿科患者的 3 期、单臂、前瞻性研究。

造血细胞移植 (HSCT) 后的类固醇难治性急性移植物抗宿主病 (SR-aGVHD) 与较差的临床结果相关。目前，尚无安全有效的疗法获准用于 12 岁以下儿科人群。因此，迫切需要安全、耐受性良好且有效管理这种使人衰弱且可能致命的 HSCT 并发症的新疗法。在早期临床试验中，间充质基质细胞 (MSC) 已证明在治疗儿科患者的急性 GVHD (aGVHD) 方面有效。我们现在报告 3 期、前瞻性、单臂、一项多中心研究 (NCT02336230) 对 54 名原发性 SR-aGVHD 儿童进行了研究，这些儿童对使用 MSC 产品 (remestemcel-L) 治疗的 aGVHD 的其他免疫抑制剂疗法是幼稚的，每周两次，剂量为 2 × 106 个细胞/kg，持续 4 周。与预先指定的对照 OR 值 45%（70.4% 对 45%，P = .0003）相比，Remestemcel-L 治疗显着提高了第 28 天的总体反应率 (OR)。统计学显着的 OR (70.4%) 持续到第 100 天，包括完全缓解从第 28 天的 29.6% 增加到第 100 天的 44.4%。总生存率在第 100 天为 74.1%，在第 180 天为 68.5%。总体反​​应在第 28 天的所有参与者中，高度预测 180 天的生存率提高，第 28 天响应者的生存率显着高于第 100 天的无响应者（86.8% 对 47. 响应者和无响应者分别为 1%，P = .0001）和第 180 天（78.9% 对 43.8%，P = .003）。Remestemcel-L 耐受性良好，未发现与输液相关的毒性或其他安全问题。这项研究提供了可靠的前瞻性证据，证明了在儿科 SR-aGVHD 中初始类固醇治疗失败后，remestemcel-L 作为一线治疗的安全性、耐受性和有效性。