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免疫检查点抑制剂治疗转移性葡萄膜黑色素瘤的综述与比较

A Review and Comparison of Immune-Checkpoint Inhibitors in the Treatment of Metastatic Uveal Melanoma.

作者信息

Alam Benyamin, Akbari Amir Reza, Ageed Ahmed, Duffy Ryan

机构信息

Queen Elizabeth Hospital, Birmingham B15 2WB, UK.

King's Mill Hospital, Sutton-in-Ashfield NG17 4JL, UK.

出版信息

J Clin Med. 2025 Jan 29;14(3):885. doi: 10.3390/jcm14030885.

Abstract

Metastatic uveal melanoma (mUM) is a rare and aggressive malignancy characterised by poor responsiveness to conventional chemotherapies, posing significant treatment challenges. Immune checkpoint inhibitor (ICI) therapies, including monotherapies with Ipilimumab, pembrolizumab, and nivolumab, as well as dual ICI therapy, have emerged as potential treatments. Whilst current research favours dual therapy over single therapy, comprehensive individualised comparisons of the efficacy and safety profiles of these therapies remain limited. This meta-analysis aims to evaluate the clinical outcomes of single ICI therapies individually and compare against combination therapy to guide optimal treatment strategies for mUM. A systematic literature review was conducted to identify studies reporting objective response rates (ORR), disease control rates (DCR), median progression-free survival (MPFS), and adverse event rates (AER) for Ipilimumab, pembrolizumab, nivolumab, and dual ICI therapy. Data were aggregated using forest plots and analysed to compare the efficacy and safety of each regimen. Dual ICI therapy demonstrated the highest ORR and DCR but showed no statistically significant advantage over monotherapies. Dual therapy also had a lower MPFS than both pembrolizumab and nivolumab monotherapies. Furthermore, dual therapy was associated with a much greater AER compared to any single therapy, including pembrolizumab and nivolumab. While dual ICI therapy offers improved ORR and DCR on aggregate analyses, monotherapies like pembrolizumab provide comparable outcomes in specific metrics, particularly MPFS, with significantly reduced toxicity. These findings underscore the need for personalised ICI regimens tailored to individual patient profiles rather than defaulting to dual therapy. Further research is essential to refine treatment guidelines and optimise outcomes for mUM patients.

摘要

转移性葡萄膜黑色素瘤(mUM)是一种罕见且侵袭性强的恶性肿瘤,其特点是对传统化疗反应不佳,带来了重大的治疗挑战。免疫检查点抑制剂(ICI)疗法,包括伊匹木单抗、帕博利珠单抗和纳武利尤单抗单药治疗以及双ICI疗法,已成为潜在的治疗方法。虽然目前的研究倾向于双药治疗而非单药治疗,但对这些疗法的疗效和安全性进行全面个体化比较仍然有限。这项荟萃分析旨在评估单ICI疗法的临床结果,并与联合疗法进行比较,以指导mUM的最佳治疗策略。进行了一项系统的文献综述,以确定报告伊匹木单抗、帕博利珠单抗、纳武利尤单抗和双ICI疗法的客观缓解率(ORR)、疾病控制率(DCR)、中位无进展生存期(MPFS)和不良事件发生率(AER)的研究。使用森林图汇总数据并进行分析,以比较每种治疗方案的疗效和安全性。双ICI疗法显示出最高的ORR和DCR,但与单药治疗相比没有统计学上的显著优势。双药治疗的MPFS也低于帕博利珠单抗和纳武利尤单抗单药治疗。此外,与任何单药治疗(包括帕博利珠单抗和纳武利尤单抗)相比,双药治疗的AER要高得多。虽然在汇总分析中双ICI疗法的ORR和DCR有所改善,但帕博利珠单抗等单药治疗在特定指标(特别是MPFS)上提供了相当的结果,且毒性显著降低。这些发现强调了需要根据个体患者情况制定个性化的ICI方案,而不是默认采用双药治疗。进一步的研究对于完善治疗指南和优化mUM患者的治疗结果至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e99c/11818147/41c56db5fa96/jcm-14-00885-g001.jpg

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