Ipilimumab in pretreated patients with metastatic uveal melanoma: safety and clinical efficacy

Abstract

Current systemic treatments for metastatic uveal melanoma (UM) have not improved overall survival (OS). The fully human anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) monoclonal antibody, ipilimumab, improved OS of patients with advanced cutaneous melanoma in a phase 3 trial; however, UM patients were excluded. The aim of this subanalysis, performed by the ipilimumab-ocular melanoma expanded access program (I-OMEAP) study group, was to assess the activity and safety of ipilimumab in patients with UM in a setting similar to daily clinical practice. Patients participating in a multicenter expanded access program (EAP) received induction treatment with ipilimumab 10 mg/kg. Maintenance doses were administered in patients who experienced clinical benefit or at physicians' discretion. Tumor assessment was evaluated per modified World Health Organization criteria at baseline, Week 12, Week 24, and Week 36. Adverse events (AEs) and immune-related AEs (irAEs) were collected according to Common Terminology Criteria for Adverse Events version 3.0. Thirteen pretreated patients with metastatic UM were treated at 6 European institutions. All patients received at least one dose of ipilimumab. Overall, no objective responses were observed; however, two patients had stable disease (SD), with a third patient achieving SD after initial progressive disease. Median OS as of July 1, 2011, was 36 weeks (range 2-172+ weeks). No grade 3/4 AEs of non-immune origin were reported. Three patients (23%) experienced grade 3 irAEs (1 thrombocytopenia, 1 diarrhea, and 1 alanine/aspartate aminotransferase elevation) that resolved with steroid therapy. The results indicate UM is a potential indication for ipilimumab treatment that should be further investigated in clinical trials.

Management of Uveal Melanoma: A Consensus-Based Provincial Clinical Practice Guideline

“…Furthermore, most systemic therapies for metastatic uveal melanoma (largely modelled after therapies for cutaneous melanoma) have failed to demonstrate clinical efficacy in phase ii trials [65][66][67][68][69][70][71][72][73][74][75][76][77][78][79][80][81] . However, immunotherapies, including the anti-ctla4 antibody ipilimumab, have shown some success in retrospective and expanded-access studies [82][83][84][85][86][87] . Pooling those publications, 188 patients with advanced uveal melanoma treated with ipilimumab experienced 1 complete response, 7 partial responses, and 52 incidences of stable disease.…”

Uveal Melanoma: A Review of the Literature

“…Several chemotherapeutic and immunomodulatory agents have been examined in patients with uveal melanoma; however, response rates have been low (less than 5%), with median overall survival ranging from 6 to 14 months [126][127][128][129][130][131][132][133][134][135][136][137].…”

Ipilimumab Activity in Advanced Uveal Melanoma: A Pooled Analysis

“…Nine articles were included in this study; including Phase II clinical trials (n = 2), Expanded Access Programs (EAP) (n = 4) and retrospective studies (n = 3) [14][15][16][17][18][19][20][21][22]. The key features of each trial are summarized in Table 1.…”