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转移性肾细胞癌患者停用免疫检查点抑制剂后疾病持久控制且并发难治性大疱性类天疱疮:一例报告。

Durable disease control and refractory bullous pemphigoid after immune checkpoint inhibitor discontinuation in metastatic renal cell carcinoma: A case report.

机构信息

Department of Medical Oncology, Institut Paoli Calmettes, Marseille, France.

Department of Urologic Surgery, Institut Paoli Calmettes, Marseille, France.

出版信息

Front Immunol. 2022 Sep 16;13:984132. doi: 10.3389/fimmu.2022.984132. eCollection 2022.

Abstract

BACKGROUND

Immune checkpoint inhibitors deeply modified metastatic renal cell carcinoma's management, and confront us to adverse events that we were not used to with conventional anti-cancer therapies. We report the case of a patient who received nivolumab as second-line treatment of a metastatic clear cell renal cell carcinoma and who developed bullous pemphigoid four years after nivolumab introduction, with persistent exacerbations even after its discontinuation.

CASE PRESENTATION

A 66-year-old man was diagnosed with lung metastasis eight years after radical nephrectomy for a clear cell renal cell carcinoma. He firstly received an anti-angiogenic agent combination, and then received anti-programmed death 1 (PD1) nivolumab as second-line treatment. Nivolumab led to prolonged disease control, but after four years of exposure the patient developed skin lesions consistent with bullous pemphigoid. After seven years of nivolumab administration and perfect disease stability, nivolumab was discontinued and surveillance was proposed. Despite nivolumab discontinuation, the patient continued to develop bullous pemphigoid exacerbations. Metastatic renal cell carcinoma was still perfectly stable more than two years after immune checkpoint discontinuation with no further anti-cancer therapy.

DISCUSSION

We report the case of a refractory bullous pemphigoid which occurred four years after nivolumab introduction and lasted despite nivolumab discontinuation, in a patient whose metastatic renal cell carcinoma is still controlled after more than two years without any anticancer treatment. This highlights the potential association between immune-related adverse events and response to immune checkpoint inhibitors, and underlines the occurrence of late-onset and long-lasting immune-related adverse events even after discontinuation of treatment, which must encourage us to remain vigilant in the long term.

摘要

背景

免疫检查点抑制剂极大地改变了转移性肾细胞癌的治疗方法,使我们面临与传统抗癌疗法不同的不良反应。我们报告了一例接受nivolumab 二线治疗转移性透明细胞肾细胞癌的患者,在接受 nivolumab 治疗四年后出现大疱性类天疱疮,即使停药后仍持续恶化。

病例介绍

一名 66 岁男性在根治性肾切除术 8 年后因透明细胞肾细胞癌发生肺转移。他首先接受了抗血管生成药物联合治疗,然后接受了抗程序性死亡 1(PD1)nivolumab 二线治疗。Nivolumab 导致疾病控制时间延长,但在暴露四年后,患者出现了与大疱性类天疱疮一致的皮肤损伤。在接受 nivolumab 治疗七年且疾病稳定后,停止了 nivolumab 治疗并提出了监测建议。尽管停止了 nivolumab,患者仍继续出现大疱性类天疱疮恶化。在停止免疫检查点治疗两年多后,转移性肾细胞癌仍然完全稳定,没有进一步的抗癌治疗。

讨论

我们报告了一例难治性大疱性类天疱疮的病例,该病例在接受 nivolumab 治疗四年后发生,尽管停止了 nivolumab 治疗,但仍持续存在,患者的转移性肾细胞癌在两年多没有任何抗癌治疗的情况下仍得到控制。这突出了免疫相关不良反应与免疫检查点抑制剂反应之间的潜在关联,并强调了即使停止治疗后也会发生迟发性和长期的免疫相关不良反应,这必须促使我们长期保持警惕。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67bb/9524245/b61b0d1d07f2/fimmu-13-984132-g001.jpg

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