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

IF 3.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY Expert Review of Clinical Pharmacology Pub Date : 2024-11-21 DOI:10.1080/17512433.2024.2431513
Joy Justice, Roma A Kankaria, Douglas B Johnson
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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.

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转移性黑色素瘤的免疫检查点抑制:在高毒性下实现高疗效。
简介免疫检查点抑制剂(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),对许多器官系统造成影响:用于控制 irAEs 的策略包括皮质类固醇、抗肿瘤坏死因子α(TNF-α)制剂、其他生物疗法、粪便微生物群移植(FMT)和新兴疗法。在这篇综述中,我们介绍了ICIs疗效、急性和慢性免疫毒性以及ICIs治疗患者毒性管理策略的现有证据:专家意见:IrAE 的管理可能会通过开发更有针对性的方法来预防毒性、改进非类固醇管理策略和调整类固醇的剂量,以及确定严重毒性的生物标志物而不断发展。
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来源期刊
Expert Review of Clinical Pharmacology
Expert Review of Clinical Pharmacology PHARMACOLOGY & PHARMACY-
CiteScore
7.30
自引率
2.30%
发文量
127
期刊介绍: Advances in drug development technologies are yielding innovative new therapies, from potentially lifesaving medicines to lifestyle products. In recent years, however, the cost of developing new drugs has soared, and concerns over drug resistance and pharmacoeconomics have come to the fore. Adverse reactions experienced at the clinical trial level serve as a constant reminder of the importance of rigorous safety and toxicity testing. Furthermore the advent of pharmacogenomics and ‘individualized’ approaches to therapy will demand a fresh approach to drug evaluation and healthcare delivery. Clinical Pharmacology provides an essential role in integrating the expertise of all of the specialists and players who are active in meeting such challenges in modern biomedical practice.
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