The management of metastatic uveal melanoma is challenging, and results following chemotherapy trials have been discouraging. There is interest in immunotherapy, and particularly systemic checkpoint inhibitors, for better control of this potentially fatal disease. Checkpoint inhibitors work at the level of the T cell, blocking built-in controls and unleashing T cells to activity. Pembrolizumab is one of several checkpoint inhibitors and specifically functions as an anti-PD-1 monoclonal antibody.
Previous studies on checkpoint inhibitors for metastatic uveal melanoma have been unimpressive. Algazi and colleagues reported results from a nine-center collaboration of 56 patients who received PD-1 or PD-L1 antibodies, 48 (86%) of which had prior therapy and only 3.6% demonstrated tumor response. These authors speculated that the low response of uveal melanoma was that it was inherently less antigenic for attraction of T cells due to its low somatic mutational burden.
In this analysis, pembrolizumab was used to treat metastatic uveal melanoma as first-line therapy in 17 patients. The authors found a response rate of 11.7%, which is lower than that of cutaneous melanoma (30% to 40%), but slightly higher than previous study on uveal melanoma (3.7%). Of the two responders, both survived with tumor control for at least 19 months. The authors studied potential factors that could identify responders from nonresponders and specifically noted no predictive factor, including expression of PD-L1 or genetic results (chromosomes three and eight).
These findings are important and a bit promising. Understanding uveal melanoma and its immune biology needs further study to better target this tumor with immunotherapy. Perhaps “inflaming” the tumor with various immunotherapeutic, chemotherapeutic or radiotherapeutic methods could promote a more robust immune response.
Algazi AP, et al. Cancer. 2016;doi:10.1002/cncr.30258.
Dalvin LA, et al. Retina. 2018;doi:10.1097/IAE.0000000000002181.
Carol L. Shields, MD
Wills Eye Hospital, Philadelphia
Disclosures: Shields reports she serves on the scientific advisory board for Aura Biosciences and Immunocore.