Department of Medicine, Nephrology, Augusta University, Medical College of Georgia, Augusta, USA.
Department of Medicine, Medical College of Georgia, Augusta, USA.
J Oncol Pharm Pract. 2021 Mar;27(2):470-476. doi: 10.1177/1078155220934160. Epub 2020 Jun 24.
Pembrolizumab is a selective anti-programmed cell death protein-1 (PD-1) humanized monoclonal antibody that inhibits PD-1 activity by binding to the PD-1 receptor that is found on activated T-cells. The goal of the treatment is to allow the immune system to target and destroy cancer cells by preventing cancer cells from binding to PD-1 receptors, leading to decreased tumor growth. The activation of T-cells by pembrolizumab not only leads to the destruction of malignant cells but also attacks the donor alloantigens that are present in a renal transplant, resulting in graft rejection.
We present a case of a 46-year-old African American female with history of renal transplant who was treated with pembrolizumab for stage IV B endometrial adenocarcinoma and experienced renal transplant rejection and severe graft intolerance syndrome. Due to ongoing graft intolerance, a transplant nephrectomy was performed. Allograft pathology was consistent with non-viable kidney with tubulitis, interstitial fibrosis and necrosis consistent with transplant rejection without any evidence of malignancy.
As emphasized in our case, there is a very high risk of graft rejection in patients who need to be placed on immunomodulators such as pembrolizumab, so the risk versus benefit needs to be assessed and discussed. Our case is unique because pembrolizumab not only caused graft rejection but also severe graft intolerance syndrome which led to transplant nephrectomy. Further guidelines are needed in renal transplant patients requiring PD-1 inhibitors to establish the ideal treatment plan of immunosuppression management and anti-cancer treatments.
帕博利珠单抗是一种选择性抗程序性细胞死亡蛋白-1（PD-1）的人源化单克隆抗体，通过与 T 细胞上发现的 PD-1 受体结合来抑制 PD-1 活性。该治疗的目的是通过阻止癌细胞与 PD-1 受体结合，从而使免疫系统能够靶向和破坏癌细胞，导致肿瘤生长减少。帕博利珠单抗激活 T 细胞不仅导致恶性细胞的破坏，还攻击存在于肾移植中的供体同种抗原，导致移植物排斥。
我们报告了一例 46 岁的非裔美国女性，患有肾移植病史，曾接受 pembrolizumab 治疗 IVB 期子宫内膜腺癌，并出现肾移植排斥和严重移植物不耐受综合征。由于持续的移植物不耐受，进行了移植肾切除术。同种异体移植病理学与 tubulitis、间质纤维化和坏死一致，与无恶性肿瘤证据的移植排斥一致，表明无活力的肾脏。
正如我们的病例所强调的那样，需要免疫调节剂（如 pembrolizumab）的患者发生移植物排斥的风险非常高，因此需要评估和讨论风险与益处。我们的病例是独特的，因为 pembrolizumab 不仅导致移植物排斥，还导致严重的移植物不耐受综合征，导致移植肾切除术。需要进一步制定肾移植患者使用 PD-1 抑制剂的指南，以建立理想的免疫抑制管理和抗癌治疗计划。
