Immune checkpoint inhibitor therapy is associated with a decreased risk of developing melanoma brain metastases

Abstract Background Despite recent advancements in metastatic melanoma treatment, the emergence of melanoma brain metastases (MBM) continues to pose a challenge. This study aimed to explore factors associated with MBM development. Methods This retrospective study included patients diagnosed with adv...

Full description

Saved in:
Bibliographic Details
Main Authors: Anna Fager, Matilda Samuelsson, Roger Olofsson Bagge, Aldina Pivodic, Sara Bjursten, Max Levin, Henrik Jespersen, Lars Ny
Format: Article
Language:English
Published: Nature Portfolio 2025-04-01
Series:BJC Reports
Online Access:https://doi.org/10.1038/s44276-025-00137-2
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850202506299179008
author Anna Fager
Matilda Samuelsson
Roger Olofsson Bagge
Aldina Pivodic
Sara Bjursten
Max Levin
Henrik Jespersen
Lars Ny
author_facet Anna Fager
Matilda Samuelsson
Roger Olofsson Bagge
Aldina Pivodic
Sara Bjursten
Max Levin
Henrik Jespersen
Lars Ny
author_sort Anna Fager
collection DOAJ
description Abstract Background Despite recent advancements in metastatic melanoma treatment, the emergence of melanoma brain metastases (MBM) continues to pose a challenge. This study aimed to explore factors associated with MBM development. Methods This retrospective study included patients diagnosed with advanced melanoma (unresectable stages III and IV [M1a-c]) between 2013 and 2019 at Sahlgrenska University Hospital, Gothenburg, Sweden. Differences in baseline and primary tumor characteristics, mutational status, biomarker levels, and first-line treatment between patients who developed MBM (BM+) and patients who did not develop MBM (BM-) were analyzed using univariable and multivariable Cox proportional hazard regression. Result Of 395 patients, 91 subsequently developed MBM. Patients who received immune checkpoint inhibitors (ICI) as first-line treatment had a reduced risk of MBM development (p ≤ 0.001). None of the eleven patients who received CTLA-4 inhibitors as monotherapy or in combination with PD-1 inhibitors as first-line treatment developed brain metastases. Elevated plasma levels of S100B (p = 0.021) and higher metastatic stage (p = 0.047) were also associated with an increased risk of MBM development. Conclusion ICI treatment is associated with a decreased risk of MBM development, suggesting a protective role. Elevated S100B levels and stage IV disease at advanced melanoma diagnosis might indicate an increased risk of MBM development.
format Article
id doaj-art-cbb93106170c4cf4a4ebc482bdbf7786
institution OA Journals
issn 2731-9377
language English
publishDate 2025-04-01
publisher Nature Portfolio
record_format Article
series BJC Reports
spelling doaj-art-cbb93106170c4cf4a4ebc482bdbf77862025-08-20T02:11:46ZengNature PortfolioBJC Reports2731-93772025-04-01311810.1038/s44276-025-00137-2Immune checkpoint inhibitor therapy is associated with a decreased risk of developing melanoma brain metastasesAnna Fager0Matilda Samuelsson1Roger Olofsson Bagge2Aldina Pivodic3Sara Bjursten4Max Levin5Henrik Jespersen6Lars Ny7Department of Oncology, Sahlgrenska University HospitalDepartment of Oncology, Sahlgrenska University HospitalDepartment of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of GothenburgAPNC SwedenDepartment of Oncology, Sahlgrenska University HospitalDepartment of Oncology, Sahlgrenska University HospitalDepartment of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy, University of GothenburgDepartment of Oncology, Sahlgrenska University HospitalAbstract Background Despite recent advancements in metastatic melanoma treatment, the emergence of melanoma brain metastases (MBM) continues to pose a challenge. This study aimed to explore factors associated with MBM development. Methods This retrospective study included patients diagnosed with advanced melanoma (unresectable stages III and IV [M1a-c]) between 2013 and 2019 at Sahlgrenska University Hospital, Gothenburg, Sweden. Differences in baseline and primary tumor characteristics, mutational status, biomarker levels, and first-line treatment between patients who developed MBM (BM+) and patients who did not develop MBM (BM-) were analyzed using univariable and multivariable Cox proportional hazard regression. Result Of 395 patients, 91 subsequently developed MBM. Patients who received immune checkpoint inhibitors (ICI) as first-line treatment had a reduced risk of MBM development (p ≤ 0.001). None of the eleven patients who received CTLA-4 inhibitors as monotherapy or in combination with PD-1 inhibitors as first-line treatment developed brain metastases. Elevated plasma levels of S100B (p = 0.021) and higher metastatic stage (p = 0.047) were also associated with an increased risk of MBM development. Conclusion ICI treatment is associated with a decreased risk of MBM development, suggesting a protective role. Elevated S100B levels and stage IV disease at advanced melanoma diagnosis might indicate an increased risk of MBM development.https://doi.org/10.1038/s44276-025-00137-2
spellingShingle Anna Fager
Matilda Samuelsson
Roger Olofsson Bagge
Aldina Pivodic
Sara Bjursten
Max Levin
Henrik Jespersen
Lars Ny
Immune checkpoint inhibitor therapy is associated with a decreased risk of developing melanoma brain metastases
BJC Reports
title Immune checkpoint inhibitor therapy is associated with a decreased risk of developing melanoma brain metastases
title_full Immune checkpoint inhibitor therapy is associated with a decreased risk of developing melanoma brain metastases
title_fullStr Immune checkpoint inhibitor therapy is associated with a decreased risk of developing melanoma brain metastases
title_full_unstemmed Immune checkpoint inhibitor therapy is associated with a decreased risk of developing melanoma brain metastases
title_short Immune checkpoint inhibitor therapy is associated with a decreased risk of developing melanoma brain metastases
title_sort immune checkpoint inhibitor therapy is associated with a decreased risk of developing melanoma brain metastases
url https://doi.org/10.1038/s44276-025-00137-2
work_keys_str_mv AT annafager immunecheckpointinhibitortherapyisassociatedwithadecreasedriskofdevelopingmelanomabrainmetastases
AT matildasamuelsson immunecheckpointinhibitortherapyisassociatedwithadecreasedriskofdevelopingmelanomabrainmetastases
AT rogerolofssonbagge immunecheckpointinhibitortherapyisassociatedwithadecreasedriskofdevelopingmelanomabrainmetastases
AT aldinapivodic immunecheckpointinhibitortherapyisassociatedwithadecreasedriskofdevelopingmelanomabrainmetastases
AT sarabjursten immunecheckpointinhibitortherapyisassociatedwithadecreasedriskofdevelopingmelanomabrainmetastases
AT maxlevin immunecheckpointinhibitortherapyisassociatedwithadecreasedriskofdevelopingmelanomabrainmetastases
AT henrikjespersen immunecheckpointinhibitortherapyisassociatedwithadecreasedriskofdevelopingmelanomabrainmetastases
AT larsny immunecheckpointinhibitortherapyisassociatedwithadecreasedriskofdevelopingmelanomabrainmetastases