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Systematic Review of the Safety of Immune Checkpoint Inhibitors Among Kidney Transplant Patients

机译:肾移植患者免疫检查点抑制剂安全性的系统评价

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IntroductionKidney 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.MethodsA 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.ResultsTwenty-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%).ConclusionThe 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.
机译:简介肾脏移植(Ktx)受体被排除在免疫检查点抑制剂的临床试验之外。该系统评价的目的是评估Ktx患者中免疫检查点抑制剂的安全性。方法从成立至2019年4月,使用MEDLINE,EMBASE和Cochrane数据库进行了文献检索。我们纳入了报告接受免疫的Ktx受体结果的研究。检查点抑制剂用于癌症治疗。结果是同种异体移植排斥和/或同种异体移植失败。结果共鉴定了27篇文章,共44例接受免疫检查点抑制剂治疗的Ktx患者。在44名Ktx患者中,有18名被报告患有急性排斥反应。从免疫检查点抑制剂到急性排斥反应诊断的中位时间为24天(四分位间距为10-60)。报告的急性同种异体移植排斥类型为细胞排斥(33%),细胞和抗体介导的混合排斥(17%)和未明确类型(50%)。 15例(83%)发生同种异体移植失败,8例(44%)死亡。 3例患者部分缓解(17%),1例患者获得了癌症缓解(6%),5例患者疾病稳定(28%)。结论我们的研究结果提高了人们对急性同种异体移植排斥/失败风险增加的认识用于Ktx患者的癌症治疗的免疫检查点抑制剂,特别是程序性细胞死亡1(PD-1)抑制剂。需要未来的大规模临床研究来评估其发病机理并计划有助于维持移植物耐受性的最佳平衡疗法。

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