Markus V Heppt1, Theresa Steeb1, Justin Gabriel Schlager1, Stefanie Rosumeck2, Corinna Dressler2, Thomas Ruzicka1, Alexander Nast2, Carola Berking3. 1. Department of Dermatology and Allergy, University Hospital, LMU Munich, Frauenlobstr. 9-11, 80337 Munich, Germany. 2. Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Dermatology, Division of Evidence - Based Medicine, Charitéplatz 1, 10117 Berlin, Germany. 3. Department of Dermatology and Allergy, University Hospital, LMU Munich, Frauenlobstr. 9-11, 80337 Munich, Germany. Electronic address: Carola.Berking@med.uni-muenchen.de.
Abstract
BACKGROUND: The use of immune checkpoint blockade (ICB) for uveal melanoma (UM) is little established. The aim of this review was to provide a comprehensive overview on the efficacy, safety, and tolerability of ICB in patients with UM. METHODS: We performed a systematic literature research covering MEDLINE, Embase and CENTRAL. Abstracts of pertinent conferences and trial registers were handsearched for relevant studies. RESULTS: Out of 1327 records initially identified, 12 eligible studies were included in the qualitative synthesis. They comprised 7 expanded access or named patient programs (n=162), 4 phase II trials (n=171), and 1 phase Ib trial (sample size unknown), while no randomized controlled trial was found. Ipilimumab monotherapy was assessed at 3mg/kg in 5 trials (n=186) with a response rate of 0 to 5%. Two reports investigated ipilimumab at 10mg/kg (n=45) with radiological responses observed in 0 to 6.5%. The median progression-free survival (PFS) was below 3months and the median overall survival was 5.2-9.8months for ipilimumab monotherapy. Severe immune-related adverse events occurred at a frequency comparable to cutaneous melanoma (6 to 36%). Two studies investigated pembrolizumab (2mg/kg) and nivolumab (3mg/kg) with overall response rates of 30% and 6%, respectively. Data on combined ipilimumab and programmed cell death protein 1 inhibition were available from one expanded access program, but no response was observed with a median PFS of 2.9months. CONCLUSIONS: UM is little responsive to ipilimumab regardless of dosage schemes. Sound randomized clinical trials are needed to evaluate the efficacy of combined ICB in patients with UM.
BACKGROUND: The use of immune checkpoint blockade (ICB) for uveal melanoma (UM) is little established. The aim of this review was to provide a comprehensive overview on the efficacy, safety, and tolerability of ICB in patients with UM. METHODS: We performed a systematic literature research covering MEDLINE, Embase and CENTRAL. Abstracts of pertinent conferences and trial registers were handsearched for relevant studies. RESULTS: Out of 1327 records initially identified, 12 eligible studies were included in the qualitative synthesis. They comprised 7 expanded access or named patient programs (n=162), 4 phase II trials (n=171), and 1 phase Ib trial (sample size unknown), while no randomized controlled trial was found. Ipilimumab monotherapy was assessed at 3mg/kg in 5 trials (n=186) with a response rate of 0 to 5%. Two reports investigated ipilimumab at 10mg/kg (n=45) with radiological responses observed in 0 to 6.5%. The median progression-free survival (PFS) was below 3months and the median overall survival was 5.2-9.8months for ipilimumab monotherapy. Severe immune-related adverse events occurred at a frequency comparable to cutaneous melanoma (6 to 36%). Two studies investigated pembrolizumab (2mg/kg) and nivolumab (3mg/kg) with overall response rates of 30% and 6%, respectively. Data on combined ipilimumab and programmed cell death protein 1 inhibition were available from one expanded access program, but no response was observed with a median PFS of 2.9months. CONCLUSIONS: UM is little responsive to ipilimumab regardless of dosage schemes. Sound randomized clinical trials are needed to evaluate the efficacy of combined ICB in patients with UM.
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