Journal
JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK
Volume 17, Issue 2, Pages 114-117Publisher
HARBORSIDE PRESS
DOI: 10.6004/jnccn.2018.7070
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Funding
- NIH/NCI [K23 CA204726]
- James C. Bradford Jr. Melanoma Fund
- NIH/NEI [5K08EY027464-02]
- Career Development Award from Research to Prevent Blindness
- Department of Defense Career Development Award [W81XWH-16-PRCRP-CDA]
- Arthur J. Schreiner Family Melanoma Research Fund
- J. Edward Mahoney Foundation Research Fund
- Brush Family Immunotherapy Fund
- Center for Research Informatics of the University of Chicago Biological Science Division
- Institute for Translational Medicine/CTSA [NIH UL1 RR024999]
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Background: 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. Methods: 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. Results: 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 MYC pathway overexpression. Conclusions: 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 MYC overexpression may be factors limiting therapeutic responses.
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