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尼伏单抗对肾移植排斥后血液透析患者的抗肿瘤活性。

Antitumor activity of nivolumab on hemodialysis after renal allograft rejection.

机构信息

Department of Medicine, The Ottawa Hospital, 501 Smyth Road, Ottawa, ON K1H 8L6 Canada ; The Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, ON K1H 8L6 Canada.

The Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, ON K1H 8L6 Canada.

出版信息

J Immunother Cancer. 2016 Oct 18;4:64. doi: 10.1186/s40425-016-0171-8. eCollection 2016.

Abstract

BACKGROUND

Nivolumab (Opdivo™) is a novel IgG4 subclass programmed death-1 (PD-1) inhibiting antibody that has demonstrated breakthrough-designation anti-tumor activity. To date, clinical trials of nivolumab and other checkpoint inhibitors have generally excluded patients with solid organ transplantation and patients with concurrent immunosuppression. However, organ transplant recipients are at high-risk of development of malignancy as a result of suppressed immune surveillance of cancer.

CASE PRESENTATION

We illustrate the outcomes of a 63 year-old type I diabetic female patient who developed pulmonary metastatic, wild-type cutaneous melanoma 10 years after renal transplantation. After downward titration of the patient's immunosuppressive medications and extensive multidisciplinary review, she was treated with nivolumab in the first-line setting. Within 1 week of administration, the patient experienced acute renal allograft rejection, renal failure and concurrent diabetic ketoacidosis due to steroid therapy. Allograft function did not return, but patient made a full clinical recovery after being placed on hemodialysis. Subsequently, the patient had clinical disease progression off therapy and required re-challenge with nivolumab on hemodialysis, resulting in ongoing clinical and radiographic response.

CONCLUSIONS

This case illustrates multiple practical challenges and dangers of administering anti-PD1 immune checkpoint inhibitors to patients with solid-organ transplantation including need for titration of immunosuppressive medications, risks of allograft rejection, and treatment during hemodialysis.

摘要

背景

纳武单抗(OpdivoTM)是一种新型 IgG4 亚型程序性死亡受体-1(PD-1)抑制剂抗体,具有突破性的抗肿瘤活性。迄今为止,纳武单抗和其他检查点抑制剂的临床试验通常排除了实体器官移植患者和同时接受免疫抑制治疗的患者。然而,器官移植受者由于癌症的免疫监视受到抑制,患恶性肿瘤的风险很高。

病例介绍

我们描述了一位 63 岁的 I 型糖尿病女性患者的治疗结果,该患者在肾移植 10 年后发生了肺部转移性、野生型皮肤黑色素瘤。在患者免疫抑制药物剂量下调并进行广泛的多学科评估后,她接受了纳武单抗一线治疗。在给药后 1 周内,患者因类固醇治疗而发生急性肾移植排斥反应、肾衰竭和并发糖尿病酮症酸中毒。尽管进行了治疗,但移植物功能仍未恢复,患者在接受血液透析治疗后完全康复。随后,患者在停止治疗后出现临床疾病进展,需要在血液透析时重新使用纳武单抗治疗,结果显示持续的临床和影像学反应。

结论

该病例说明了向实体器官移植患者使用抗 PD-1 免疫检查点抑制剂时存在多种实际挑战和危险,包括需要调整免疫抑制药物剂量、移植排斥反应的风险以及血液透析期间的治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6dd/5067882/809fb56d09d7/40425_2016_171_Fig1_HTML.jpg

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