The use of pembrolizumab for the treatment of metastatic uveal melanoma

Abstract

Uveal melanoma is a rare type of melanoma, with only five to seven cases per one million persons diagnosed each year. Patients with metastatic melanoma of uveal origin tend to have lower response rates on traditional therapies. Herein we report our experience with 10 patients with metastatic uveal melanoma (MUM) who received pembrolizumab. Eligible patients were more than or equal to 18 years old, had unresectable MUM, progressed on prior ipilimumab therapy, had good performance status (Eastern Cooperative Oncology Group of 0 or 1), and adequate organ and marrow function. Patients could have central nervous system disease, but needed to be clinically stable. Patients were treated with 2 mg/kg pembrolizumab intravenously over 30 min every 3 weeks until disease progression, unacceptable toxicity, or for up to 2 years. Between April 2014 and October 2014, we treated a total of 10 patients with MUM with pembrolizumab. Median age was 65 years, with 70% being female. As of the data cutoff date of 14 May 2015, median progression-free survival was 18 weeks (range 3.14-49.3 weeks), with four patients still currently receiving therapy. Of eight evaluable patients, there was one complete response, two partial responses, and one patient with stable disease. Four patients had rapidly progressive disease. Toxicities were as expected and were usually grade 1/2 in nature. Although this cohort of patients was small, to our knowledge this is the first such report of outcomes in uveal melanoma patients being treated with anti-PD1 therapy. In the absence of a clinical trial, treatment with pembrolizumab appears to be a viable option for patients with MUM.

Anti-PD1 treatment in metastatic uveal melanoma in the Netherlands

“…The median PFS was 18 weeks with four patients still ongoing treatment, which is high compared to the 10.3 weeks (2.3 months) in our cohort, indicating strong patient selection [13]. Our study differed from the research by Kottschade et al because we included patients with WHO performance score of 2.…”

PD-L1 Expression in Tumor Metastasis is Different Between Uveal Melanoma and Cutaneous Melanoma

“…MUM patients are often treated with immune checkpoint inhibitors identical to those used in the treatment of MCM (anti-programmed death-1 [PD-1] and anti-CTLA4 [Cytotoxic T-lymphocyte-associated protein 4] antibodies), either as monotherapy or in combination. Contrary to MCM, MUM demonstrates a poor response to these immune checkpoint blockades [15] (Table 1) [16][17][18][19][20][21][22][23] One of the mechanisms by which tumors evade the immune system is through upregulation and expression of PD-L1 protein on their surface. PD-L1 on tumor cells interacts with PD-1 receptor expressed on activated T cells, leading to T-cell exhaustion, anergy and ultimately, immune response abandonment [24,25].…”

Ipilimumab Activity in Advanced Uveal Melanoma: A Pooled Analysis

“…More recently, there have been studies with anti-programmed cell death protein 1 antibody (anti-PD1) monotherapy and targeted therapy with MEK inhibitors that have demonstrated some activity [23][24][25]. Although at least one small series has observed activity with pembrolizumab, more extensive experience suggests that responses and clinical benefit are much more limited than with advanced cutaneous melanoma [23,24].…”

“…Although at least one small series has observed activity with pembrolizumab, more extensive experience suggests that responses and clinical benefit are much more limited than with advanced cutaneous melanoma [23,24]. The role of the newer agents in the treatment landscape for advanced UM needs to be determined and clinically justified bearing in mind the toxicity seen especially with targeted therapy [25].…”