title: 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.
authors.affiliation: Medical Oncology and Immunotherapy Unit, University Hospital of Siena, Istituto Toscano Tumori, Strada delle Scotte, 53100 Siena, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Danielli
authors.forename: Ruggero
authors.initials: R
authors.lastname: Ridolfi
authors.forename: Vanna
authors.initials: V
authors.lastname: Chiarion-Sileni
authors.forename: Paola
authors.initials: P
authors.lastname: Queirolo
authors.forename: Alessandro
authors.initials: A
authors.lastname: Testori
authors.forename: Ruth
authors.initials: R
authors.lastname: Plummer
authors.forename: Monica
authors.initials: M
authors.lastname: Boitano
authors.forename: Luana
authors.initials: L
authors.lastname: Calabrò
authors.forename: Costanza De
authors.initials: CD
authors.lastname: Rossi
authors.forename: Anna Maria Di
authors.initials: AM
authors.lastname: Giacomo
authors.forename: Pier Francesco
authors.initials: PF
authors.lastname: Ferrucci
authors.forename: Laura
authors.initials: L
authors.lastname: Ridolfi
authors.forename: Maresa
authors.initials: M
authors.lastname: Altomonte
authors.forename: Clelia
authors.initials: C
authors.lastname: Miracco
authors.forename: Angelo
authors.initials: A
authors.lastname: Balestrazzi
authors.forename: Michele
authors.initials: M
authors.lastname: Maio
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D060908:CTLA-4 Antigen / Q000276:immunology; D018450:Disease Progression; D005260:Female; D006801:Humans; D000074324:Ipilimumab; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D008875:Middle Aged; D009362:Neoplasm Metastasis; D014604:Uveal Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D000098943:Uveal Melanoma
chemical_list: D000911:Antibodies, Monoclonal; D060908:CTLA-4 Antigen; D000074324:Ipilimumab