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免疫检查点抑制剂在血液系统恶性肿瘤中的毒性

Toxicity of Immune-Checkpoint Inhibitors in Hematological Malignancies.

作者信息

Hradska Katarina, Hajek Roman, Jelinek Tomas

机构信息

Department of Haematooncology, University Hospital Ostrava, Ostrava, Czechia.

Faculty of Medicine, University of Ostrava, Ostrava, Czechia.

出版信息

Front Pharmacol. 2021 Aug 13;12:733890. doi: 10.3389/fphar.2021.733890. eCollection 2021.

Abstract

Immune checkpoint inhibitors (ICIs), especially those targeting the programmed-death 1 (PD-1) receptor and its ligands, have become indispensable agents in solid tumor anti-cancer therapy. Concerning hematological malignancies, only nivolumab and pembrolizumab have been approved for the treatment of relapsed and refractory classical Hodgkin lymphoma and primary mediastinal large B cell lymphoma to date. Nevertheless, clinical research in this field is very active. The mechanism of action of ICIs is based on unblocking the hindered immune system to recognize and eliminate cancer cells, but that also has its costs in the form of ICI-specific immune related adverse events (irAEs), which can affect any organ system and can even be lethal. In this article, we have reviewed all prospective blood cancer clinical trials investigating ICIs (both monotherapy and combination therapy) with available toxicity data with the purpose of determining the incidence of irAEs in this specific setting and to offer a brief insight into their management, as the use of immune checkpoint blockade is not so frequent in hemato-oncology.

摘要

免疫检查点抑制剂(ICIs),尤其是那些靶向程序性死亡1(PD-1)受体及其配体的抑制剂,已成为实体瘤抗癌治疗中不可或缺的药物。关于血液系统恶性肿瘤,迄今为止,只有纳武单抗和派姆单抗被批准用于治疗复发难治性经典霍奇金淋巴瘤和原发性纵隔大B细胞淋巴瘤。然而,该领域的临床研究非常活跃。ICIs的作用机制是基于解除受阻的免疫系统对癌细胞的识别和清除,但这也会以ICI特异性免疫相关不良事件(irAEs)的形式产生代价,这些不良事件可影响任何器官系统,甚至可能致命。在本文中,我们回顾了所有研究ICIs(单药治疗和联合治疗)的前瞻性血液癌症临床试验,并提供了可用的毒性数据,目的是确定在这一特定情况下irAEs的发生率,并简要介绍其管理方法,因为免疫检查点阻断在血液肿瘤学中的应用并不常见。

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