Safety and Efficacy of Ipilimumab plus Nivolumab and Sequential Selective Internal Radiation Therapy in Hepatic and Extrahepatic Metastatic Uveal Melanoma.

Veronica Aedo-Lopez,Olivier Michielin,Michel A Cuendet,Camille L Gérard,Bianca Gautron Moura,Gregoire Berthod,Antonia Digklia,Sarah Boughdad,Rafael Duran,Krisztian Homicsko,Niklaus Schaefer

doi:10.3390/cancers14051162

Abstract

Simple SummaryDespite recent progress on the treatment of metastatic uveal melanoma (mUM), prognosis remains dismal for the majority of patients. Directed liver therapies including selective internal radiation therapy (SIRT) have been the pillar of hepatic metastases management. Independently, immune checkpoint blockade by combination of ipilimumab plus nivolumab has demonstrated a median survival slightly superior to 1 year. However, the benefit of sequential ipilimumab plus nivolumab immunotherapy and SIRT has not been elucidated.To assess the safety and efficacy of ipilimumab plus nivolumab around selective internal radiation therapy (SIRT) in patients with metastatic uveal melanoma (mUM). We present a retrospective, single center study of 32 patients with mUM divided into two groups based on the treatment received between April 2013 and April 2021. The SIRT_IpiNivo cohort was treated with Yttrium-90 microspheres and ipilimumab plus nivolumab before or after the SIRT (n = 18). The SIRT cohort underwent SIRT but did not receive combined immunotherapy with ipilimumab plus nivolumab (n = 14). Twelve patients (66.7%) of the SIRT_IpiNivo arm received SIRT as first-line treatment and six patients (33.3%) received ipilimumab plus nivolumab prior to SIRT. In the SIRT group, seven patients (50.0%) received single-agent immunotherapy. One patient treated with combined immunotherapy 68 months after the SIRT was included in this group. At the start of ipilimumab plus nivolumab, 94.4% (n = 17) presented hepatic metastases and 72.2% (n = 13) had extra liver disease. Eight patients (44.4%) of the SIRT_IpiNivo group experienced grade 3 or 4 immune related adverse events, mainly colitis and hepatitis. Median overall survival from the diagnosis of metastases was 49.6 months (95% confidence interval (CI); 24.1-not available (NA)) in the SIRT_IpiNivo group compared with 13.6 months (95% CI; 11.5-NA) in the SIRT group (log-rank p-value 0.027). The presence of extra liver metastases at the time of SIRT, largest liver lesion more than 8 cm (M1c) and liver tumor volume negatively impacted the survival. This real-world cohort suggests that a sequential treatment of ipilimumab plus nivolumab and SIRT is a well-tolerated therapeutic approach with promising survival rates.

Highlights

Uveal melanoma (UM) is a rare cancer with an incidence in Europe that varies from 8 per million in Northern countries such as Norway or Denmark [1]
This study describes the safety and efficacy of sequential combination of ipilimumab plus nivolumab and selective internal radiation therapy (SIRT) in patients with metastatic uveal melanoma (mUM) compared with SIRT without combined immunotherapy
We conclude that combined immunotherapy before or after the SIRT is a safe therapeutic option and appears to be associated with improved survival rates

Summary

Introduction

Uveal melanoma (UM) is a rare cancer with an incidence in Europe that varies from 8 per million in Northern countries such as Norway or Denmark [1]. It is the most frequent primary intraocular malignancy. Different systemic treatments have been studied including chemotherapy, targeted therapy and immunotherapy but standard of care does not exist for metastatic uveal melanoma (mUM) patients yet. Tebentafusp, a bispecific antibody that redirects T cell lysis of melanoma cells expressing gp100, demonstrated a prolonged overall survival (OS) as first-line therapy for mUM patients with HLA-A*02:01 compared to investigator’s choice (IC), either pembrolizumab, ipilimumab or dacarbazine [17]

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