aDepartment of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
bDepartment of Medicine, University of Chicago, Chicago, Illinois.
J Natl Compr Canc Netw. 2019 Feb;17(2):114-117. doi: 10.6004/jnccn.2018.7070.
Uveal melanoma (UM) is an uncommon melanoma subtype with poor prognosis. Agents that have transformed the management of cutaneous melanoma have made minimal inroads in UM. We conducted a single-arm phase II study of pembrolizumab in patients with metastatic UM and performed bioinformatics analyses of publicly available datasets to characterize the activity of anti-PD-1 in this setting and to understand the mutational and immunologic profile of this disease. A total of 5 patients received pembrolizumab in this study. Median overall survival was not reached, and median progression-free survival was 11.0 months. One patient experienced a complete response after one dose and 2 others experienced prolonged stable disease (20% response rate, 60% clinical benefit rate); 2 additional patients had rapidly progressing disease. Notably, the patients who benefited had either no liver metastases or small-volume disease, whereas patients with rapidly progressing disease had bulky liver involvement. We performed a bioinformatics analysis of The Cancer Genome Atlas for UM and confirmed a low mutation burden and low rates of T-cell inflammation. Note that the lack of T-cell inflammation strongly correlated with pathway overexpression. Anti-PD-1-based therapy may cause clinical benefit in metastatic UM, seemingly more often in patients without bulky liver metastases. Lack of mutation burden and T-cell infiltration and overexpression may be factors limiting therapeutic responses. NCT02359851.
葡萄膜黑色素瘤（UM）是一种预后不良的罕见黑色素瘤亚型。改变皮肤黑色素瘤治疗方法的药物在 UM 中的作用甚微。我们对转移性 UM 患者进行了 pembrolizumab 的单臂 II 期研究，并对公开可用的数据集进行了生物信息学分析，以表征该环境中抗 PD-1 的活性，并了解该疾病的突变和免疫特征。共有 5 名患者在这项研究中接受了 pembrolizumab 治疗。中位总生存期未达到，中位无进展生存期为 11.0 个月。一名患者在接受一剂治疗后出现完全缓解，另外两名患者出现长期稳定疾病（20%的缓解率，60%的临床获益率）；另外两名患者疾病迅速进展。值得注意的是，受益的患者要么没有肝转移，要么只有少量疾病，而疾病迅速进展的患者肝内受累体积较大。我们对 UM 的癌症基因组图谱进行了生物信息学分析，证实了低突变负担和低 T 细胞炎症率。请注意，缺乏 T 细胞炎症与 通路过表达强烈相关。基于抗 PD-1 的治疗可能在转移性 UM 中引起临床获益，在没有大体积肝转移的患者中似乎更为常见。缺乏突变负担、T 细胞浸润和 过表达可能是限制治疗反应的因素。NCT02359851。
