文章：

恶性胸膜间皮瘤的当前最先进疗法及以免疫治疗为核心的未来选择

Current State-of-the-Art Therapy for Malignant Pleural Mesothelioma and Future Options Centered on Immunotherapy

原文发布日期：10 December 2023

DOI: 10.3390/cancers15245787

类型: Article

开放获取: 是

英文摘要：

Malignant pleural mesothelioma (MPM) is a locally aggressive disease related to asbestos exposure with a median survival for untreated patients of 4–8 months. The combination of chemotherapy based on platinum and antifolate is the standard treatment, and the addition of bevacizumab adds two months to median survival. Recently, in first-line treatment, immunotherapy combining nivolumab with ipilimumab has been shown to be superior to chemotherapy in the CheckMate-743 study in terms of overall survival (18.1 months), leading to its approval by the FDA and EMA. The positive results of this study represent a new standard of treatment for patients with MPM; however, not all patients will benefit from immunotherapy treatment. In an effort to improve the selection of patient candidates for immunotherapy for different tumors, biomarkers that have been associated with a greater possibility of response to treatment have been described. MPM is a type of tumor with low mutational load and neo-antigens, making it a relatively non-immunogenic tumor for T cells and possibly less susceptible to responding to immunotherapy. Different retrospective studies have shown that PD-L1 expression occurs in 20–40% of patients and is associated with a poor prognosis; however, the predictive value of PD-L1 in response to immunotherapy has not been confirmed. The purpose of this work is to review the state of the art of MPM treatment in the year 2023, focusing on the efficacy results of first-line or subsequent immunotherapy studies on patients with MPM and possible chemo-immunotherapy combination strategies. Additionally, potential biomarkers of response to immunotherapy will be reviewed, such as histology, PD-L1, lymphocyte populations, and TMB.

摘要翻译： 

恶性胸膜间皮瘤（MPM）是一种与石棉暴露相关的局部侵袭性疾病，未经治疗患者的中位生存期为4-8个月。基于铂类和抗叶酸药物的化疗是标准治疗方案，而添加贝伐珠单抗可将中位生存期延长两个月。近期，CheckMate-743研究显示，在一线治疗中纳武利尤单抗联合伊匹木单抗的免疫疗法在总生存期（18.1个月）方面优于化疗，该方案已获得美国食品药品监督管理局和欧洲药品管理局批准。该研究的积极成果为MPM患者建立了新的治疗标准，但并非所有患者都能从免疫治疗中获益。为优化不同肿瘤患者免疫治疗的筛选标准，目前已发现多种与治疗应答可能性相关的生物标志物。MPM是一种突变负荷和新抗原水平较低的肿瘤类型，使其成为对T细胞相对非免疫原性的肿瘤，可能对免疫治疗的反应较弱。多项回顾性研究表明，20-40%的患者存在PD-L1表达，且与不良预后相关，但PD-L1对免疫治疗反应的预测价值尚未得到证实。本文旨在综述2023年MPM治疗的最新进展，重点关注MPM患者一线或后续免疫治疗研究的疗效结果，以及可能的化疗-免疫联合治疗策略。同时，将探讨免疫治疗反应的潜在生物标志物，包括组织学类型、PD-L1表达、淋巴细胞亚群和肿瘤突变负荷。

原文链接：

Current State-of-the-Art Therapy for Malignant Pleural Mesothelioma and Future Options Centered on Immunotherapy