Research progress of immune checkpoint inhibitors in the treatment of acral melanoma

Jiajia QIAN; Cong RUAN; Jiyong LIU; Rui XU

doi:10.19401/j.cnki.1007-3639.2025.07.009

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Research progress of immune checkpoint inhibitors in the treatment of acral melanoma

Review | 更新时间：2025-12-31

- Research progress of immune checkpoint inhibitors in the treatment of acral melanoma
- China Oncology Vol. 35, Issue 7, Pages: 702-709(2025)
- 作者机构：
  
  1. 复旦大学附属肿瘤医院闵行院区药剂科，上海 200240
  2. 复旦大学附属肿瘤医院药剂科，复旦大学上海医学院肿瘤学系，上海 200032
- 作者简介：
- 基金信息：
  
  Excellent Young Pharmacy Talent Program of Minhang District Health System, Shanghai(mwyjyx03);Natural Science Research of Minhang District, Shanghai(2023MHZ096)
- DOI：10.19401/j.cnki.1007-3639.2025.07.009
  CLC： R739.5
- Received：19 November 2024，
  
  Revised：2025-06-17，
  
  Published：30 July 2025
- 稿件说明：
移动端阅览
Jiajia QIAN, Cong RUAN, Jiyong LIU, et al. Research progress of immune checkpoint inhibitors in the treatment of acral melanoma[J]. China Oncology, 2025, 35(7): 702-709.
DOI：

Jiajia QIAN, Cong RUAN, Jiyong LIU, et al. Research progress of immune checkpoint inhibitors in the treatment of acral melanoma[J]. China Oncology, 2025, 35(7): 702-709. DOI： 10.19401/j.cnki.1007-3639.2025.07.009.

摘要

近年来，免疫检查点抑

制剂（immune checkpoint inhibitor，ICI）在复发或转移性晚期皮肤黑色素瘤（cutaneous melanoma，CM）的治疗中取得重大进展，能够显著延长患者的总生存期。但由于不同黑色素瘤亚型的生物学特性的差异导致免疫应答程度不尽相同，其中中国的主要亚型肢端型黑色素瘤（acral melanoma，AM）患者从ICI治疗中获益相对有限，特别是仅接受免疫单药治疗时。目前全球尚缺乏针对AM的统一分期分型标准及规范化治疗方案，ICI在AM罕见亚型中的临床应用证据仍然不足。在新辅助治疗中，多项国际上大型Ⅱ/Ⅲ期针对CM的临床试验（如SWOG 1801、NADINA）表明，ICI新辅助联合治疗可以显著提高CM患者的病理学缓解率。而AM新辅助治疗仍处于探索阶段，对于可切除的Ⅲ/Ⅳ期患者，特瑞普利单抗联合溶瘤病毒或卡瑞利珠单抗联合阿帕替尼和替莫唑胺治疗已显示出潜力，但长期生存获益还需要更长时间及更大样本量的临床研究来证实。在辅助治疗方面，针对

BRAF

突变AM患者，来自中国的真实世界研究证实达拉非尼联合曲美替尼与程序性死亡蛋白-1（programmed death-1，PD-1）抑制剂单药用于治疗高风险可切除的Ⅲ/Ⅳ期黑色素瘤患者的生存率差异无统计学意义，但目前尚缺乏头对头的比较；对于可切除的Ⅲ/Ⅳ期

BRAF

野生型AM患者，PD-1抑制剂联合辅助治疗比单药更能够减少复发风险，并能够提高生存率。在晚期治疗方面，无论是帕博利珠单抗，还是特瑞普利单抗和普特利单抗，在中国人群中开展的临床试验疗效均较低。ICI联合其他治疗策略（包括联合化疗、抗血管生成药物、双免疫或3种免疫）可以改善肿瘤微环境，预后更明确，但安全性还有待评估；针对ICI耐药的AM患者，目前正在探索和验证多种治疗方案，如免疫联合治疗、靶向治疗和化疗。此外，一系列新兴免疫疗法[T细胞受体工程改造、肿瘤疫苗、嵌合抗原受体T（chimeric antigen receptor T，CAR-T）细胞疗法、抗体药物偶联物（antibody drug conjugate，ADC）

]

也正在研发中。本综述聚焦于ICI在AM治疗中的临床研究进展，涵盖新辅助治疗、辅助治疗及晚期治疗各阶段的疗效证据与安全性评价，并探讨潜在生物标志物和联合治疗策略，旨在为临床实践提供理论支持和研究方向。

Abstract

In recent years

immune checkpoint inhibitor (ICI) has led to substantial advances in the treatment of recurrent or metastatic advanced cutaneous melanoma (CM)

significantly prolonging overall survival. However

due to the biological heterogeneity across melanoma subtypes

the degree of immune responsiveness varies considerably. In particular

acral melanoma (AM) (the predominant melanoma subtype in Asian populations

including China) has demonstrated limited benefit from ICI therapy

especially in the context of monotherapy. Currently

no systematic staging and standardized treatment guidelines are available for AM

and clinical evidence supporting the use of ICI in this rare subtype remains insufficient. In the neoadjuvant setting

several large phase Ⅱ/Ⅲ international trials in CM

including SWOG 1801 and NADINA

have shown that ICI-based neoadjuvant combination therapy significantly improves pathological response rates compar

ed with traditional adjuvant approaches. Nevertheless

neoadjuvant treatment in AM remains in the exploratory stage. Early-phase clinical studies in resectable stage Ⅲ/Ⅳ AM suggest that toripalimab combined with intratumoral oncolytic virus therapy

or camrelizumab in combination with apatinib and temozolomide

may offer clinical benefit; however

confirmation of long-term survival benefit requires further validation in larger

prospective cohorts. In the adjuvant setting

for AM patients with

BRAF

mutations

real-world data from China have shown no significant difference in survival outcomes between dabrafenib plus trametinib and programmed death-1 (PD-1) inhibitor monotherapy in high-risk resectable stage Ⅲ/Ⅳ disease

although direct head-to-head comparisons are lacking. For patients with resectable stage Ⅲ/Ⅳ wild-type AM

combination adjuvant regimens incorporating PD-1 inhibitors may provide superior recurrence risk reduction and survival benefit compared to monotherapy. In the advanced disease setting

in Chinese populations

the objective response rates of PD-1 inhibitors such as pembrolizumab

toripalimab and penpulimab remain suboptimal in AM. ICI-based combination strategies (including those with chemotherapy

anti-angiogenic agents

dual or triple immune checkpoint blockade) may improve the immune microenvironment and clinical prognosis

but concerns regarding safety and tolerability persist. For patients with ICI-refractory AM

various novel approaches combining immunotherapy

targeted agents and chemotherapy are under investigation. Additionally

several next-generation immunotherapeutic modalities [including T-cell receptor-engineered (TCR-T) therapies

therapeutic cancer vaccines

chimeric antigen receptor T (CAR-T) cell therapy and antibody-drug conjugate (ADC)

]

are currently in development. This review aimed to provide a comprehensive overview of current clinical evidence on the use of ICI in acral melanoma across the neoadjuvant

adjuvant

and advanced disease settings. We highli

ghted the efficacy and safety of existing strategies

exploreed emerging combination regimens and predictive biomarkers

and discussed key areas for future research to inform clinical decision-making and optimize outcomes in this challenging melanoma subtype.

关键词

Keywords

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