Manohar Sandhya, Thongprayoon Charat, Cheungpasitporn Wisit, Markovic Svetomir N, Herrmann Sandra M
Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA.
Division of Nephrology, Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi, USA.
Kidney Int Rep. 2019 Dec 7;5(2):149-158. doi: 10.1016/j.ekir.2019.11.015. eCollection 2020 Feb.
Kidney transplant (Ktx) recipients are excluded from clinical trials of immune checkpoint inhibitors. The aim of this systematic review was to assess the safety of immune checkpoint inhibitors among Ktx patients.
A literature search was conducted using MEDLINE, EMBASE, and Cochrane Database from inception through April 2019. We included studies that reported outcomes of Ktx recipients who received immune checkpoint inhibitors for cancer treatment. Outcomes of interest were allograft rejection and/or allograft failure.
Twenty-seven articles with a total of 44 Ktx patients treated with immune checkpoint inhibitor were identified. Of 44 Ktx patients, 18 were reported to have acute rejection. Median time from immune checkpoint inhibitors to acute rejection diagnosis was 24 (interquartile range, 10-60) days. Reported types of acute allograft rejection were cellular rejection (33%), mixed cellular and antibody-mediated rejection (17%), and unspecified type (50%). Fifteen (83%) had allograft failure and 8 (44%) died. Three patients had a partial remission (17%), 1 patient achieved cancer response (6%), and 5 patients had stable disease (28%).
The findings of our study raise awareness of the increased risk for acute allograft rejection/failure following immune checkpoint inhibitors for cancer treatment among Ktx patients, in particular with programmed cell death 1 (PD-1) inhibitors. Future large-scale clinical studies are required to appraise the pathogenesis and plan optimal balanced therapy that helps sustain graft tolerance.
肾移植(Ktx)受者被排除在免疫检查点抑制剂的临床试验之外。本系统评价的目的是评估免疫检查点抑制剂在Ktx患者中的安全性。
使用MEDLINE、EMBASE和Cochrane数据库从创刊至2019年4月进行文献检索。我们纳入了报告接受免疫检查点抑制剂治疗癌症的Ktx受者结局的研究。感兴趣的结局是移植肾排斥和/或移植肾失功。
共识别出27篇文章,涉及44例接受免疫检查点抑制剂治疗的Ktx患者。在44例Ktx患者中,有18例报告发生急性排斥反应。从免疫检查点抑制剂治疗至急性排斥反应诊断的中位时间为24天(四分位间距,10 - 60天)。报告的急性移植肾排斥反应类型为细胞性排斥(33%)、细胞和抗体介导的混合性排斥(17%)以及未明确类型(50%)。15例(83%)发生移植肾失功,8例(44%)死亡。3例患者部分缓解(17%),1例患者癌症有反应(6%),5例患者病情稳定(28%)。
我们的研究结果提高了对Ktx患者在接受免疫检查点抑制剂治疗癌症后急性移植肾排斥/失功风险增加的认识,尤其是程序性细胞死亡蛋白1(PD - 1)抑制剂。未来需要大规模临床研究来评估发病机制并制定有助于维持移植肾耐受的最佳平衡治疗方案。