Jagasia Madan, Zeiser Robert, Arbushites Michael, Delaite Patricia, Gadbaw Brian, Bubnoff Nikolas von
Vanderbilt-Ingram Cancer Center, 1301 Medical Center Dr #1710, Nashville, TN, USA 37232.
Department of Hematology, Oncology & Stem Cell Transplantation, University Hospital Freiburg, Hugstetter Str. 55, 79106 Freiburg im Breisgau, Germany.
Immunotherapy. 2018 Apr;10(5):391-402. doi: 10.2217/imt-2017-0156. Epub 2018 Jan 10.
For patients with hematologic malignancies and disorders, allogeneic hematopoietic stem cell transplantation offers a potentially curative treatment option. Many patients develop graft-versus-host disease (GVHD), a serious complication and leading cause of nonrelapse mortality. Corticosteroids are the standard first-line treatment for GVHD; however, patients often become steroid-refractory or remain corticosteroid-dependent. New second-line treatment options are needed to improve patient outcomes. Here we review the role of JAK1 and JAK2 in acute and chronic GVHD. We also describe the study designs of the Phase II REACH1 (NCT02953678) and the Phase III REACH2 (NCT02913261) and REACH3 (NCT03112603) clinical trials that are currently recruiting patients to evaluate the JAK1/JAK2 inhibitor ruxolitinib in patients with corticosteroid-refractory acute or chronic GVHD.
对于血液系统恶性肿瘤和疾病患者而言，异基因造血干细胞移植提供了一种潜在的治愈性治疗选择。许多患者会发生移植物抗宿主病（GVHD），这是一种严重的并发症，也是非复发死亡率的主要原因。皮质类固醇是GVHD的标准一线治疗药物；然而，患者常常会出现类固醇难治性情况或持续依赖皮质类固醇。需要新的二线治疗选择来改善患者的治疗效果。在此，我们综述了JAK1和JAK2在急性和慢性GVHD中的作用。我们还描述了目前正在招募患者的II期REACH1（NCT02953678）、III期REACH2（NCT02913261）和REACH3（NCT03112603）临床试验的研究设计，这些试验旨在评估JAK1/JAK2抑制剂芦可替尼用于皮质类固醇难治性急性或慢性GVHD患者的疗效。
