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

SIMPLE SUMMARY: Despite 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, imm...

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Autores principales: Aedo-Lopez, Veronica, Gérard, Camille L., Boughdad, Sarah, Gautron Moura, Bianca, Berthod, Gregoire, Digklia, Antonia, Homicsko, Krisztian, Schaefer, Niklaus, Duran, Rafael, Cuendet, Michel A., Michielin, Olivier
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8909598/
https://www.ncbi.nlm.nih.gov/pubmed/35267470
http://dx.doi.org/10.3390/cancers14051162
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author Aedo-Lopez, Veronica
Gérard, Camille L.
Boughdad, Sarah
Gautron Moura, Bianca
Berthod, Gregoire
Digklia, Antonia
Homicsko, Krisztian
Schaefer, Niklaus
Duran, Rafael
Cuendet, Michel A.
Michielin, Olivier
author_facet Aedo-Lopez, Veronica
Gérard, Camille L.
Boughdad, Sarah
Gautron Moura, Bianca
Berthod, Gregoire
Digklia, Antonia
Homicsko, Krisztian
Schaefer, Niklaus
Duran, Rafael
Cuendet, Michel A.
Michielin, Olivier
author_sort Aedo-Lopez, Veronica
collection PubMed
description SIMPLE SUMMARY: Despite 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. ABSTRACT: 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.
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spelling pubmed-89095982022-03-11 Safety and Efficacy of Ipilimumab plus Nivolumab and Sequential Selective Internal Radiation Therapy in Hepatic and Extrahepatic Metastatic Uveal Melanoma Aedo-Lopez, Veronica Gérard, Camille L. Boughdad, Sarah Gautron Moura, Bianca Berthod, Gregoire Digklia, Antonia Homicsko, Krisztian Schaefer, Niklaus Duran, Rafael Cuendet, Michel A. Michielin, Olivier Cancers (Basel) Article SIMPLE SUMMARY: Despite 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. ABSTRACT: 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. MDPI 2022-02-24 /pmc/articles/PMC8909598/ /pubmed/35267470 http://dx.doi.org/10.3390/cancers14051162 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Aedo-Lopez, Veronica
Gérard, Camille L.
Boughdad, Sarah
Gautron Moura, Bianca
Berthod, Gregoire
Digklia, Antonia
Homicsko, Krisztian
Schaefer, Niklaus
Duran, Rafael
Cuendet, Michel A.
Michielin, Olivier
Safety and Efficacy of Ipilimumab plus Nivolumab and Sequential Selective Internal Radiation Therapy in Hepatic and Extrahepatic Metastatic Uveal Melanoma
title Safety and Efficacy of Ipilimumab plus Nivolumab and Sequential Selective Internal Radiation Therapy in Hepatic and Extrahepatic Metastatic Uveal Melanoma
title_full Safety and Efficacy of Ipilimumab plus Nivolumab and Sequential Selective Internal Radiation Therapy in Hepatic and Extrahepatic Metastatic Uveal Melanoma
title_fullStr Safety and Efficacy of Ipilimumab plus Nivolumab and Sequential Selective Internal Radiation Therapy in Hepatic and Extrahepatic Metastatic Uveal Melanoma
title_full_unstemmed Safety and Efficacy of Ipilimumab plus Nivolumab and Sequential Selective Internal Radiation Therapy in Hepatic and Extrahepatic Metastatic Uveal Melanoma
title_short Safety and Efficacy of Ipilimumab plus Nivolumab and Sequential Selective Internal Radiation Therapy in Hepatic and Extrahepatic Metastatic Uveal Melanoma
title_sort safety and efficacy of ipilimumab plus nivolumab and sequential selective internal radiation therapy in hepatic and extrahepatic metastatic uveal melanoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8909598/
https://www.ncbi.nlm.nih.gov/pubmed/35267470
http://dx.doi.org/10.3390/cancers14051162
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