Ruxolitinib as Salvage Therapy for Chronic Graft-versus-Host Disease
Ruxolitinib as Salvage Therapy for Chronic Graft-versus-Host Disease
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DOI：
10.1016/j.bbmt.2018.09.003
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发表时间：
2019-02-01
影响因子：
4.3
通讯作者：
Nakamura, Ryotaro
中科院分区：
文献类型：
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作者：
Modi, Badri;Hernandez-Henderson, Michael;Nakamura, Ryotaro
慢性移植物抗宿主病（cGVHD）仍然是异基因造血细胞移植后的主要并发症，显著影响患者的生活质量。全身性皮质类固醇方案被认为是一线治疗，但通常与反应不足和多种副作用相关。在难治性疾病患者中，缺乏基于证据的共识，以单一的最佳方法来管理症状。Ruxolitinib是一种选择性JAK 1/2抑制剂，最近在类固醇难治性cGVHD患者中作为二线方法获得青睐。在这项回顾性研究中，我们评估了2016年3月至2017年12月期间在我们机构接受ruxolitinib治疗cGVHD的46例患者的结局，并根据美国国立卫生研究院严重程度量表评估了ruxolitinib在6个月和12个月时的影响，包括器官特异性反应和平均泼尼松剂量。此外，我们首次报道了ruxolitinib在cGVHD患者中的无治疗失败生存率（FFS）。ruxolitinib治疗12个月后，分别在13%（n = 6）、30.4%（n =14）和10.9%（n = 5）的患者中观察到完全缓解、部分缓解和疾病稳定。FFS的1年概率为54.2%（95%置信区间，0.388至0.673），使用ruxolitinib与泼尼松剂量减少相关。总之，我们的数据代表了迄今为止报告的最大cGVHD患者队列，支持使用鲁索利替尼治疗类固醇难治性cGVHD和目前可用的挽救治疗，由于缺乏反应和高成本而停止。(C)2018年美国血液和骨髓移植协会。
Chronic graft-versus-host disease (cGVHD) continues to be a major complication after allogeneic hematopoietic cell transplantation, significantly affecting patients' quality of life. A regimen of systemic corticosteroids is considered first-line therapy but is often associated with inadequate responses and multiple side effects. In patients with refractory disease, an evidenced-based consensus is lacking as to the single best approach to managing symptoms. Ruxolitinib, a selective JAK1/2 inhibitor, has recently gained favor as a second-line approach in patients with steroid-refractory cGVHD. In this retrospective study, we evaluated the outcomes of 46 patients who received ruxolitinib for cGVHD between March 2016 and December 2017 at our institution, and evaluated ruxolitinib's impact at 6 and 12 months, based on the National Institutes of Health Severity Scale, including organ-specific responses, and mean prednisone dose. Furthermore, we present the first reported probability of ruxolitinib's treatment failure-free survival (FFS) in patients with cGVHD. After 12 months of ruxolitinib therapy, complete response, partial response, and stable disease was observed in 13% (n = 6), 30.4% (n =14), and 10.9% (n = 5) of patients, respectively. The 1-year probability of FFS was 54.2% (95% confidence interval, .388 to .673), and ruxolitinib use was associated with a reduction in prednisone dose. In conclusion, our data, which represent the largest cohort of patients with cGVHD reported to date, support the use of ruxolitinib for cGVHD refractory to steroids and currently available salvage therapies, discontinued due to lack of response and high cost. (C) 2018 American Society for Blood and Marrow Transplantation.