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转移性黑色素瘤的免疫检查点抑制:在高毒性情况下实现高效能。

Immune checkpoint inhibition of metastatic melanoma: achieving high efficacy in the face of high toxicity.

作者信息

Justice Joy, Kankaria Roma A, Johnson Douglas B

机构信息

Vanderbilt University School of Medicine, Nashville, TN, USA.

Department of Medicine, Vanderbilt-Ingram Cancer Center, Nashville, TN, USA.

出版信息

Expert Rev Clin Pharmacol. 2024 Dec;17(12):1115-1125. doi: 10.1080/17512433.2024.2431513. Epub 2024 Nov 21.

Abstract

INTRODUCTION

Immune checkpoint inhibitors (ICIs) have advanced the treatment of metastatic melanoma by blocking immune system down-regulators enhancing T-cell-mediated anti-tumor responses. However, many ICIs induce immune-related adverse effects (irAEs) that can impact many organ systems.

AREAS COVERED

Strategies used to manage irAEs include corticosteroids, anti-tumor necrosis factor alpha (TNF-α) agents, other biological therapies, fecal microbiota transplantation (FMT), and emerging regimens. In this review, we describe current evidence for the efficacy of ICIs, acute and chronic immune toxicities, and strategies to manage toxicities for patients treated with ICIs.

EXPERT OPINION

IrAE management will likely evolve by developing more tailored approaches to prevent toxicities, improving non-steroidal management strategies and tailoring the dose of steroids, and identifying biomarkers of severe toxicities.

摘要

引言

免疫检查点抑制剂(ICIs)通过阻断免疫系统下调因子,增强T细胞介导的抗肿瘤反应,推动了转移性黑色素瘤的治疗。然而,许多ICIs会诱发免疫相关不良反应(irAEs),可影响多个器官系统。

涵盖领域

用于管理irAEs的策略包括皮质类固醇、抗肿瘤坏死因子α(TNF-α)药物、其他生物疗法、粪便微生物群移植(FMT)以及新兴方案。在本综述中,我们描述了ICIs疗效、急慢性免疫毒性以及管理接受ICIs治疗患者毒性的策略的当前证据。

专家观点

IrAE管理可能会通过开发更具针对性的方法来预防毒性、改进非甾体管理策略并调整类固醇剂量以及识别严重毒性的生物标志物而不断演变。

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