Outcome of Patients with Delayed Brain Metastases Following Initial Ipilimumab plus Nivolumab Treatment of Disseminated Melanoma

Abstract Introduction: Patients with metastatic melanoma have an elevated risk of developing brain metastases. Treatment with immune checkpoint inhibitors appears to decrease this risk. Methods: A retrospective analysis of uncommon patients with delayed onset of brain metastases following first-line ipilimumab plus nivolumab treatment for metastatic cutaneous melanoma was performed. Patient characteristics and outcomes were analysed, as was the effectiveness of salvage therapy. Results: Of 75 metastatic melanoma patients who received first-line ipilimumab/nivolumab treatment, 7 (9.3%) developed subsequent new brain metastases. The incidence was 13.8% in patients receiving standard regimen of ipilimumab/nivolumab and 7.1% in patients receiving the alternate dosing schedule. Median time to onset of brain metastases from the start of therapy was 4.8 months. The median survival was only 8.4 months, despite attempted salvage therapy. Conclusion: Treatment with ipilimumab and nivolumab seems to result in a reduced incidence of brain metastases in metastatic melanoma patients. Most of these recurrences were identified during the first year of immunotherapy. The apparent reduction of the brain metastasis by the alternate ipilimumab/nivolumab dosing regimen requires further confirmation. All patients with delayed onset brain metastases died. Thus, more effective treatment options for brain metastases that occur during immunotherapy are badly needed.