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Introduction Immune Checkpoint Inhibitors (ICI) have revolutionised management of many cancers, but are associated with treatment-limiting immunotherapy-related adverse events (IRAE). Gamma-Knife Radiosurgery (GK) is an effective, minimally-invasive intervention for primary and secondary brain tumours. As more patients are offered combinations of these treatments, greater clarity is required on potential complications.Methods This retrospective cohort study identified 239 patients with malignant melanoma (MM) receiving ICI, between 2019-2023, at a tertiary oncology centre, through electronic care records. Data was collated on timing, duration and types of treatments, along with diagnosis, type and onset of IRAE.Results 67.3% of all patients had IRAE; the 44 patients who also received GK for cerebral metastases had significantly higher rates of IRAE than those receiving immunotherapy alone (86.4% vs 63.1%). GK prior to completing immunotherapy resulted in increased rates of IRAE (83.9% vs 25%) and reduced time to IRAE onset (50 vs 232 days), compared to GK after immunotherapy was completed.Discussion To our knowledge this is the first study to highlight the potential increased risk of IRAE in patients receiving combined radio-immunotherapy. As more trials investigate the role of immunotherapy in managing primary and secondary brain tumours, further consideration should be given to these potentially treatment-limiting complications.f.vansomeren@nhs.net