PD-1/PD-L1抑制剂可以用于合并自身免疫病的患者吗？ | 引经据典[15] · 协和呼吸

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PD-1/PD-L1抑制剂治疗合并自身免疫病的非小细胞肺癌患者的分析

Safety of Programmed Death–1 Pathway Inhibitors Among Patients With Non–Small-Cell Lung Cancer and Preexisting Autoimmune Disorders

关键词

非小细胞肺癌，PD-1/PD-L1抑制剂，自身免疫病

作者：

Leonardi GC, et. al

翻译：

北京协和医院呼吸内科  张 宇  黄 慧

文献来源：

J Clin Oncol. 2018;36(19):1905-1912.

DOI:

10.1200/JCO.2017.77.0305.

  背景及目的  

PD-1/PD-L1抑制剂目前已广泛用于治疗晚期非小细胞肺癌（NSCLC）患者，但相关的临床试验在招募过程中，排除大多数合并自身免疫性疾病（AID）的晚期NSCLC患者。因此，合并AID的NSCLC患者接受上述免疫治疗的疗效、安全性尚不明确。

  方   法  

本研究回顾性分析了针对合并自身免疫性疾病的晚期NSCLC患者接受PD-1/PD-L1抑制剂治疗的相关资料，其中自身免疫性疾病涉及风湿免疫病，以及神经系统、内分泌系统、胃肠道系统和皮肤等领域的自身免疫病。

  结    果  

1、共纳入PD-1/PD-L1抑制剂治疗合并AID的晚期NSCLC患者56例。在治疗起始阶段，10例患者（18%）有AID活动期症状，11例患者（20%）正在接受针对AID的激素/免疫制剂的治疗。

2、PD-1/PD-L1抑制剂治疗后，31例患者（55%）出现了原有AID的恶化和/或本免疫治疗相关不良事件（irAE）。其中13名患者（23%）出现了原有AID加重，4例需要系统性糖皮质激素（以下简称激素）治疗。

3、共23例次（21例，两例发生两次irAE）（38%）出现irAE：其中17例次(74%)为1-2级irAE，3-4级irAE为6例次(26%)，其中7例患者需要加用激素治疗。因irAE终止PD-1/ PD-L1抑制剂治疗的患者8例（14%）。

4、56例患者中,NSCLC的总缓解率为22%。

表 56例非小细胞肺癌患者的自身免疫性疾病类型

  结    论  

对于合并AID的晚期NSCLC患者，经PD-1/PD-L1抑制剂治疗后仅有少部分患者发生基础AID的加重，irAE发生率与不合并AID的NSCLC患者差不多；仅有很少一部分患者因irAE而终止PD-1/PD-L1抑制剂治疗。

原文摘要

Purpose 

Although programmed death (PD)-1 pathway inhibitors are now used in nearly all patients with advanced non-small-cell lungcancer (NSCLC), the large number of patients with NSCLC and concurrent autoimmune disease (AID) have been universally excluded from immunotherapy clinical trials. Therefore, the safety of PD-1 and PD-ligand 1 (PD-L1) inhibitors in patients with NSCLC and underlying AID is currently unknown.

Methods

As part of a multi-institutional effort, we retrospectively collected clinicopathologic data from patients with NSCLC and a history of AID who received monotherapy with either a PD-1 or a PD-L1 (herein referred to as PD-[L]1) inhibitor. Qualifying AIDs included but were not limited to: rheumatologic, neurologic, endocrine, GI, and dermatologic conditions.

Results

We identified 56 patients with NSCLC and an AID who received a PD-(L)1 inhibitor. At the time of treatment initiation, 18% of patients had active AID symptoms and 20% were receiving immunomodulatory agents for their AID. A total of 55% of patients developed an AID flare and/or an immune-related adverse event (irAE). Exacerbation of the AID occurred in 13 patients (23% of the whole cohort), four of whom required systemic corticosteroids. Immune-related adverse events occurred in 21 patients (38%). Among irAEs, 74% were grade 1 or 2 and 26% were grade 3 or 4; eight patients required corticosteroids for irAE management. PD-(L)1 therapy was permanently discontinued in eight patients (14%) because of irAEs. The overall response rate to immunotherapy in this population was 22%.

Conclusion

In patients with NSCLC with AID treated with a PD-(L)1 inhibitor, exacerbation of AID occurred in a minority of patients. The incidence of irAEs was similar to reported rates in clinical trials where patients with AID were excluded. Adverse events were generally manageable and infrequently led to permanent discontinuation of immunotherapy.

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作者介绍

张 宇

北京协和医院呼吸内科硕士在读

北京协和医院呼吸内科2016级硕士研究生，所在课题组主要从事呼吸系统恶性肿瘤内科治疗方面的临床和基础研究。

往期经典

文字来源：张 宇   黄 慧

栏目负责：黄    慧

版面编辑：陈珂琪

图片来源：部分来源于网络，如有侵权，请联系删除

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