Peripheral Biomarkers and Determinants of Survival for Patients with Melanoma Brain Metastasis Treated with Immune Checkpoint Blockade
- 1University of Oxford
Abstract
BackgroundImmune checkpoint blockade (ICB) has become the standard of treatment for metastatic melanoma (MM). However, patients with melanoma brain metastases (MBM) are often excluded from clinical trials. Here we analyse patients within the real-world OxCITE cohort receiving ICB treatment for metastatic melanoma, with a focus on MBM, aiming to discern outcomes, prognostic factors and peripheral biomarkers.
MethodsPatients eligible for ICB treatment were recruited prospectively. Demographic, clinical and radiological data were collected from electronic patient records. Plasma samples were collected prior to the first cycle of treatment for plasma proteomic analysis.
Results307 patients were included, 81 of whom had MBM on commencing ICB. No difference in overall survival between patients with and without brain metastases was noted on multivariable analysis (HR=1.1, 95% CI 0.73-1.6, p=0.68), whereas hepatic metastases were associated with increased risk of death (HR 1.7, 95% CI 1.2-2.4, p=0.0019). Within the MBM group, steroid treatment (HR=2.5, 95% CI 1.3-5.0, p=0.006) was associated with poor OS, whilst treatment with single agent ICB (HR=1.9, 95% CI 0.86-3.9, p=0.11), symptomatic first presentation of MBM (HR=1.5, 95% CI 0.76-2.8, p=0.25) and anti-seizure drug treatment (HR=1.74, 95% CI 0.89-3.4, p=0.10) were not. Amongst all patients carriage of a BRAF mutation was associated with increased risk of MBM (OR 2.49, 95% CI 1.4-4.4, p=0.0007), and increased propensity to new brain metastases on ICB treatment (OR 2.5, 95% CI 1.1-5.9, p=0.036). Analysis of blood and plasma samples demonstrated that patients with MBM have altered haematological profiles, with raised NLR and increased plasma glial fibrillary acidic protein levels, reinforcing the distinct systemic features of MBM.
ConclusionsIn this real-world cohort of patients receiving ICB for metastatic melanoma, the presence of MBM did not associate with worse OS. Conversely, baseline corticosteroid use was adversely prognostic. Intriguingly, plasma GFAP was significantly elevated in patients with MBM and correlated with the burden of intracranial disease, highlighting a potential role for GFAP as a candidate biomarker for MBM in high-risk surveillance. Our observations indicate the adversely prognostic weight historically attached to M1d disease is no longer applicable in the ICB era.
Related
- Immune checkpoint blockade activates macrophages and remodels the lymph node microenvironment in melanoma metastasis
- Editorial: Predictive biomarkers to immune checkpoint inhibitors in lung cancer
- Beyond PD-L1: emerging clinical and molecular biomarkers of response to immune checkpoint inhibitors in non-small cell lung cancer
- Long-term survival with immune checkpoint inhibitors combined with bevacizumab in advanced clear cell renal cell carcinoma : A case report
- Cancer type-specific profiling of chromatin regulator mutations identifies recurrent and co-occurring gene sets associated with improved survival following immune checkpoint therapy
BibTeX
@misc{hassan2026peripheral,
title = {{Peripheral Biomarkers and Determinants of Survival for Patients with Melanoma Brain Metastasis Treated with Immune Checkpoint Blockade}},
author = {J. Hassan and M. Little and A. Farkas and S. Mackay and N. Coupe and M. Middleton and M. J. Payne and B. Fairfax},
howpublished = {medRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.19.26365947},
url = {https://www.medrxiv.org/content/10.64898/2026.10.19.26365947v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Peripheral Biomarkers and Determinants of Survival for Patients with Melanoma Brain Metastasis Treated with Immune Checkpoint Blockade
AU - J. Hassan
AU - M. Little
AU - A. Farkas
AU - S. Mackay
AU - N. Coupe
AU - M. Middleton
AU - M. J. Payne
AU - B. Fairfax
PY - 2026
DA - 2026/10/19
PB - medRxiv
DO - 10.64898/2026.10.19.26365947
UR - https://www.medrxiv.org/content/10.64898/2026.10.19.26365947v1
AB - BackgroundImmune checkpoint blockade (ICB) has become the standard of treatment for metastatic melanoma (MM). However, patients with melanoma brain metastases (MBM) are often excluded from clinical trials. Here we analyse patients within the real-world OxCITE cohort receiving ICB treatment for metastatic melanoma, with a focus on MBM, aiming to discern outcomes, prognostic factors and peripheral biomarkers. MethodsPatients eligible for ICB treatment were recruited prospectively. Demographic, clinical and radiological data were collected from electronic patient records. Plasma samples were collected prior to the first cycle of treatment for plasma proteomic analysis. Results307 patients were included, 81 of whom had MBM on commencing ICB. No difference in overall survival between patients with and without brain metastases was noted on multivariable analysis (HR=1.1, 95% CI 0.73-1.6, p=0.68), whereas hepatic metastases were associated with increased risk of death (HR 1.7, 95% CI 1.2-2.4, p=0.0019). Within the MBM group, steroid treatment (HR=2.5, 95% CI 1.3-5.0, p=0.006) was associated with poor OS, whilst treatment with single agent ICB (HR=1.9, 95% CI 0.86-3.9, p=0.11), symptomatic first presentation of MBM (HR=1.5, 95% CI 0.76-2.8, p=0.25) and anti-seizure drug treatment (HR=1.74, 95% CI 0.89-3.4, p=0.10) were not. Amongst all patients carriage of a BRAF mutation was associated with increased risk of MBM (OR 2.49, 95% CI 1.4-4.4, p=0.0007), and increased propensity to new brain metastases on ICB treatment (OR 2.5, 95% CI 1.1-5.9, p=0.036). Analysis of blood and plasma samples demonstrated that patients with MBM have altered haematological profiles, with raised NLR and increased plasma glial fibrillary acidic protein levels, reinforcing the distinct systemic features of MBM. ConclusionsIn this real-world cohort of patients receiving ICB for metastatic melanoma, the presence of MBM did not associate with worse OS. Conversely, baseline corticosteroid use was adversely prognostic. Intriguingly, plasma GFAP was significantly elevated in patients with MBM and correlated with the burden of intracranial disease, highlighting a potential role for GFAP as a candidate biomarker for MBM in high-risk surveillance. Our observations indicate the adversely prognostic weight historically attached to M1d disease is no longer applicable in the ICB era.
ER -