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[默克尔细胞癌中的免疫检查点抑制]

[Immune checkpoint inhibition in Merkel cell carcinoma].

作者信息

Terheyden P, Mohr A, Langan E A

机构信息

Klinik für Dermatologie, Universität zu Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Deutschland.

Dermatological Science, University of Manchester, Manchester, Großbritannien.

出版信息

Hautarzt. 2019 Sep;70(9):684-690. doi: 10.1007/s00105-019-4465-x.

Abstract

BACKGROUND

Merkel cell carcinoma (MCC) is a rare but aggressive form of skin cancer in which Merkel cell polyomavirus infection and chronic exposure to ultraviolet radiation are key risk factors. Immune checkpoint inhibition has revolutionized the treatment of locally advanced, inoperable and metastatic MCC.

AIM

To outline the modern management of MCC based on advances in our understanding of MCC tumour biology and the development of immune checkpoint inhibitors, namely inhibitors of programmed cell death protein (PD)-1- and PD‑1 ligand 1 (PD-L1).

METHODS

A review of the scientific literature listed in PubMed.

RESULTS

First line therapy with the PD-L1 blocking antibody avelumab is associated with a response rate of 62%. In the second line setting, for example after chemotherapy, the response rate only reaches 33%. However, in patients who responded in the second line setting, 69% remained relapse free after 2 years. Treatment responses occurred on average after 6.1 weeks of therapy. First line treatment with pembrolizumab (anti-PD‑1 antibody) is associated with a 2-year survival rate of 69% and the median survival rate has not been reached. Whilst the various chemotherapy regimens are associated with similar response rates, these are typically short lived.

DISCUSSION

Checkpoint inhibition offers an effective treatment option for patients with MCC. Avelumab is currently licensed as a treatment for metastatic disease. Chemotherapy remains an option to reduce tumor load, or in the context of resistance and/or contraindications to immune checkpoint therapy. Adjuvant and neoadjuvant use of checkpoint inhibition in MCC may represent a future treatment strategy pending the results of on-going clinical trials.

摘要

背景

默克尔细胞癌(MCC)是一种罕见但侵袭性强的皮肤癌,其中默克尔细胞多瘤病毒感染和长期暴露于紫外线辐射是关键危险因素。免疫检查点抑制已彻底改变了局部晚期、无法手术和转移性MCC的治疗方式。

目的

基于我们对MCC肿瘤生物学的理解进展以及免疫检查点抑制剂(即程序性细胞死亡蛋白(PD)-1和PD-1配体1(PD-L1)抑制剂)的开发,概述MCC的现代管理方法。

方法

对PubMed列出的科学文献进行综述。

结果

使用PD-L1阻断抗体阿维鲁单抗进行一线治疗的缓解率为62%。在二线治疗中,例如化疗后,缓解率仅达到33%。然而,在二线治疗有反应的患者中,69%在2年后仍无复发。治疗反应平均在治疗6.1周后出现。使用派姆单抗(抗PD-1抗体)进行一线治疗的2年生存率为69%,中位生存期尚未达到。虽然各种化疗方案的缓解率相似,但通常持续时间较短。

讨论

检查点抑制为MCC患者提供了一种有效的治疗选择。阿维鲁单抗目前被批准用于治疗转移性疾病。化疗仍然是降低肿瘤负荷的一种选择,或者在对免疫检查点治疗耐药和/或有禁忌的情况下使用。在MCC中辅助和新辅助使用检查点抑制可能代表一种未来的治疗策略,有待正在进行的临床试验结果。

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