硬化性慢性移植物抗宿主病 (cGVHD) 是一种高度发病且难治的 cGVHD，迫切需要针对硬化性 cGVHD 的新疗法。本研究旨在确定鲁索替尼对皮质类固醇难治性硬化性 cGVHD 患者的疗效。在一项单臂多中心 II 期试验（N = 47）中，患有皮质类固醇难治性硬化性 cGVHD 且接受了至少 1 种额外的 cGVHD 全身治疗的成人患者鲁索替尼治疗≥6 个月（ClinicalTrials.gov 标识符：NCT03616184）。主要终点是根据 2014 年美国国立卫生研究院 cGVHD 共识标准定义的皮肤和/或关节完全或部分缓解 (PR)。使用鲁索替尼中位 11 个月后，皮肤和/或关节出现 PR 6 个月时，49% 的患者（95% CI，34 至 64）出现此症状，其中 45% 的患者出现关节和筋膜反应，19% 的患者出现皮肤反应。 12 个月时皮肤/关节反应的持续时间为 77%（95% CI，48 至 91）。总体 cGVHD PR 率为 47%（95% CI，32 至 61）。 38% 的患者的 Lee 症状量表总结和皮肤分量表评分有所改善。治疗失败的累积发生率为 20.8%（95% CI，10.0 至 34.1），非复发死亡率 (NRM) 为 2.2%（95% CI，0.17 至 10.3），无复发恶性肿瘤，无失败生存期 (FFS) 12 个月时为 77.1%（95% CI，61.3 至 87.0）。鲁索替尼总体耐受性良好，没有新的安全信号。使用鲁索替尼与难治性硬化性 cGVHD 患者相对较高的皮肤/关节反应率和总体 cGVHD 反应率、患者报告结果的改善、低 NRM 和高 FFS 相关。鲁索替尼为难治性硬化性 cGVHD 提供了有效的治疗选择。

Sclerotic chronic graft-versus-host disease (cGVHD) represents a highly morbid and refractory form of cGVHD, and novel therapies for sclerotic cGVHD are critically needed. This study aimed to determine the efficacy of ruxolitinib in patients with corticosteroid refractory sclerotic cGVHD.In a single-arm multicenter phase II trial (N = 47), adults with sclerotic cGVHD refractory to corticosteroids and ≥one additional line of systemic therapy for cGVHD received ruxolitinib for ≥six months (ClinicalTrials.gov identifier: NCT03616184). The primary end point was complete or partial response (PR) in skin and/or joint defined according to the 2014 National Institute of Health cGVHD Consensus Criteria.Following the use of ruxolitinib for a median of 11 months, PR in skin and/or joints was noted in 49% (95% CI, 34 to 64) at 6 months, with 45% having joint and fascia response and 19% having skin response. The duration of skin/joint response was 77% (95% CI, 48 to 91) at 12 months. Overall cGVHD PR was noted in 47% (95% CI, 32 to 61). Improvement in Lee Symptom Scale summary and skin subscale scores was noted in 38% of patients. With a cumulative incidence of treatment failure of 20.8% (95% CI, 10.0 to 34.1), nonrelapse mortality (NRM) of 2.2% (95% CI, 0.17 to 10.3), and no recurrent malignancy, failure-free survival (FFS) was 77.1% (95% CI, 61.3 to 87.0) at 12 months. Ruxolitinib was overall well tolerated with no new safety signals.The use of ruxolitinib was associated with relatively high rates of skin/joint responses and overall cGVHD responses, improvement in patient-reported outcomes, low NRM, and high FFS in patients with refractory sclerotic cGVHD. Ruxolitinib offers an effective treatment option for refractory sclerotic cGVHD.