Wu Hengwei, Shi Jimin, Luo Yi, Tan Yamin, Zhang Mingming, Lai Xiaoyu, Yu Jian, Liu Lizhen, Fu Huarui, Huang He, Zhao Yanmin
Bone Marrow Transplantation Center, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China.
Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China.
JAMA Netw Open. 2021 Jan 4;4(1):e2034750. doi: 10.1001/jamanetworkopen.2020.34750.
Ruxolitinib, a selective inhibitor of the Janus kinases 1/2 signaling pathway, has shown a significant response in steroid-refractory chronic graft-vs-host disease (SR-cGVHD), a major cause of morbidity and mortality in individuals who have undergone allogeneic hematopoietic stem cell transplantation (HSCT).
To investigate the clinical response to ruxolitinib in patients with SR-cGVHD after allogeneic HSCT and to evaluate its safety profile during the treatment course.
DESIGN, SETTING, AND PARTICIPANTS: This single-center case series included 41 consecutive patients who were treated with ruxolitinib for SR-cGVHD after allogeneic HSCT between August 2017 and December 2019. Data were collected from each patient's medical record at the First Affiliated Hospital of Zhejiang University School of Medicine. Data analysis was conducted from March to May 2020.
Ruxolitinib.
Treatment responses, factors associated with response, and adverse effects during ruxolitinib administration.
Overall, 41 patients (median [range] age, 31 [17-56] years; 14 [34.1%] women) were treated with ruxolitinib and included in this study. A total of 15 patients (36.6%) had a complete remission, and 14 (34.1%) had a partial remission, with an overall response rate of 70.7% (29 patients; 95% CI, 56.2%-85.3%). Lung involvement (odds ratio, 0.112; 95% CI, 0.020-0.639; P = .01) and matched related donors (odds ratio, 0.149; 95% CI, 0.022-0.981; P = .048) were associated with less favorable treatment response. Major adverse events associated with ruxolitinib were cytopenias and infectious complications. The median (range) follow-up for this cohort was 14.9 (1.4-32.5) months. Prolonged survival was observed in patients with a male donor (P = .006), complete remission before transplantation (P = .02), baseline moderate cGVHD (P = .02), and skin cGVHD (P = .001).
In this small, single-site case series, ruxolitinib demonstrated a significant response in heavily pretreated patients with SR-cGVHD and a reasonably well-tolerated safety profile. The results add to the body of literature suggesting ruxolitinib as a promising treatment option in SR-cGVHD.
芦可替尼是一种Janus激酶1/2信号通路的选择性抑制剂，在类固醇难治性慢性移植物抗宿主病（SR-cGVHD）中已显示出显著疗效，SR-cGVHD是接受异基因造血干细胞移植（HSCT）患者发病和死亡的主要原因。
研究异基因HSCT后SR-cGVHD患者对芦可替尼的临床反应，并评估其治疗过程中的安全性。
设计、地点和参与者：本单中心病例系列研究纳入了2017年8月至2019年12月期间接受芦可替尼治疗SR-cGVHD的41例连续患者。数据收集自浙江大学医学院附属第一医院每位患者的病历。数据分析于2020年3月至5月进行。
芦可替尼。
芦可替尼给药期间的治疗反应、与反应相关的因素及不良反应。
总体而言，41例患者（年龄中位数[范围]为31[17 - 56]岁；14例[34.1%]为女性）接受了芦可替尼治疗并纳入本研究。共有15例患者（36.6%）完全缓解，14例（34.1%）部分缓解，总缓解率为70.7%（29例患者；95%CI，56.2% - 85.3%）。肺部受累（比值比，0.112；95%CI，0.020 - 0.639；P = 0.01）和匹配的相关供体（比值比，0.149；95%CI，0.022 - 0.981；P = 0.048）与较差的治疗反应相关。与芦可替尼相关的主要不良事件是血细胞减少和感染并发症。该队列的中位（范围）随访时间为14.9（1.4 - 32.5）个月。男性供体患者（P = 0.006）、移植前完全缓解（P = 0.02）、基线中度cGVHD（P = 0.02）和皮肤cGVHD（P = 0.001）患者的生存期延长。
在这个小型单中心病例系列中，芦可替尼在重度预处理的SR-cGVHD患者中显示出显著疗效且安全性耐受性良好。这些结果进一步丰富了相关文献，表明芦可替尼是SR-cGVHD中一种有前景的治疗选择。
