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

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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.

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