Response to Anti-PD-1 in Uveal Melanoma Without High-Volume Liver Metastasis.

Johnson DB, Bao R, Ancell KK, Daniels AB, Wallace D, Sosman JA, Luke JJ
J Natl Compr Canc Netw. 2019 17 (2): 114-117

PMID: 30787124 · 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.

Copyright © 2019 by the National Comprehensive Cancer Network.

MeSH Terms (12)

Antineoplastic Agents, Immunological Computational Biology Gene Expression Profiling Humans Liver Neoplasms Melanoma Molecular Targeted Therapy Neoplasm Staging Prognosis Programmed Cell Death 1 Receptor Treatment Outcome Uveal Neoplasms

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