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恶性胸膜间皮瘤的当前先进疗法及以免疫疗法为中心的未来选择

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

作者信息

Cedres Susana, Valdivia Augusto, Iranzo Patricia, Callejo Ana, Pardo Nuria, Navarro Alejandro, Martinez-Marti Alex, Assaf-Pastrana Juan David, Felip Enriqueta, Garrido Pilar

机构信息

Medical Oncology Department, Vall d´Hebron Institute of Oncology (VHIO), Vall d'Hebron Hospital Universitari, 08035 Barcelona, Spain.

Thoracic Cancers Translational Genomics Unit, Medical Oncology Department, Vall d´Hebron Institute of Oncology (VHIO), Vall d´Hebron Hospital Universitari, 08035 Barcelona, Spain.

出版信息

Cancers (Basel). 2023 Dec 10;15(24):5787. doi: 10.3390/cancers15245787.


DOI:10.3390/cancers15245787
PMID:38136333
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10741743/
Abstract

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

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,未经治疗的患者中位生存期为4至8个月。基于铂和抗叶酸的化疗联合是标准治疗方法,添加贝伐单抗可使中位生存期延长两个月。最近,在一线治疗中,纳武单抗与伊匹木单抗联合的免疫疗法在CheckMate-743研究中显示,就总生存期(18.1个月)而言优于化疗,从而获得了美国食品药品监督管理局(FDA)和欧洲药品管理局(EMA)的批准。这项研究的阳性结果代表了MPM患者的一种新治疗标准;然而,并非所有患者都能从免疫疗法治疗中获益。为了改进针对不同肿瘤的免疫疗法患者候选者的选择,已经描述了与更高治疗反应可能性相关的生物标志物。MPM是一种具有低突变负荷和新抗原的肿瘤类型,使其对T细胞而言是相对缺乏免疫原性的肿瘤,可能对免疫疗法反应较差。不同的回顾性研究表明,20%至40%的患者存在程序性死亡受体配体1(PD-L1)表达,且与不良预后相关;然而,PD-L1在免疫疗法反应中的预测价值尚未得到证实。这项工作的目的是回顾2023年MPM治疗的最新状况,重点关注MPM患者一线或后续免疫疗法研究的疗效结果以及可能的化疗-免疫疗法联合策略。此外,将回顾免疫疗法反应的潜在生物标志物,如组织学、PD-L1、淋巴细胞群体和肿瘤突变负荷(TMB)。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03f2/10741743/9ed2f6c8cd91/cancers-15-05787-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03f2/10741743/9ed2f6c8cd91/cancers-15-05787-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03f2/10741743/9ed2f6c8cd91/cancers-15-05787-g001.jpg

相似文献

[1]
Current State-of-the-Art Therapy for Malignant Pleural Mesothelioma and Future Options Centered on Immunotherapy.

Cancers (Basel). 2023-12-10

[2]
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J Transl Med. 2021-5-31

[3]
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Ann Oncol. 2022-5

[4]
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[5]
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[6]
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[7]
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[9]
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[10]
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引用本文的文献

[1]
Malignant Pleural Mesothelioma: From Pathophysiology to Innovative Actionable Targets.

Cancers (Basel). 2025-3-30

[2]
An Overview of Cellular and Molecular Determinants Regulating Chemoresistance in Pleural Mesothelioma.

Cancers (Basel). 2025-3-14

[3]
Malignant pleural mesothelioma treated with cytoreductive video-assisted thoracic surgery plus hyperthermic intrathoracic chemotherapy: a case report.

J Thorac Dis. 2024-11-30

[4]
Phase I Clinical Trial on Pleural Mesothelioma Using Neoadjuvant Local Administration of Paclitaxel-Loaded Mesenchymal Stromal Cells (PACLIMES Trial): Study Rationale and Design.

Cancers (Basel). 2024-10-4

本文引用的文献

[1]
Pembrolizumab plus chemotherapy versus chemotherapy in untreated advanced pleural mesothelioma in Canada, Italy, and France: a phase 3, open-label, randomised controlled trial.

Lancet. 2023-12-16

[2]
ONCOS-102 plus pemetrexed and platinum chemotherapy in malignant pleural mesothelioma: a randomized phase 2 study investigating clinical outcomes and the tumor microenvironment.

J Immunother Cancer. 2023-9

[3]
Brief Report: Canadian Cancer Trials Group IND.227: A Phase 2 Randomized Study of Pembrolizumab in Patients With Advanced Malignant Pleural Mesothelioma (NCT02784171).

J Thorac Oncol. 2023-6

[4]
Immune Checkpoint Inhibitors in Malignant Pleural Mesothelioma: A Systematic Review and Meta-Analysis.

Cancers (Basel). 2022-12-9

[5]
Comprehensive genomic and tumour immune profiling reveals potential therapeutic targets in malignant pleural mesothelioma.

Genome Med. 2022-5-30

[6]
Epithelioid Pleural Mesothelioma Is Characterized by Tertiary Lymphoid Structures in Long Survivors: Results from the MATCH Study.

Int J Mol Sci. 2022-5-21

[7]
The Predictive and Prognostic Nature of Programmed Death-Ligand 1 in Malignant Pleural Mesothelioma: A Systematic Literature Review.

JTO Clin Res Rep. 2022-3-22

[8]
First-line nivolumab plus ipilimumab versus chemotherapy for the treatment of unresectable malignant pleural mesothelioma: patient-reported outcomes in CheckMate 743.

Lung Cancer. 2022-5

[9]
Anetumab ravtansine versus vinorelbine in patients with relapsed, mesothelin-positive malignant pleural mesothelioma (ARCS-M): a randomised, open-label phase 2 trial.

Lancet Oncol. 2022-4

[10]
First-line nivolumab plus ipilimumab versus chemotherapy in patients with unresectable malignant pleural mesothelioma: 3-year outcomes from CheckMate 743.

Ann Oncol. 2022-5

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