Résumé
Background and purpose: patients with melanoma brain metastases (MBM) represent a particular group in terms of treatment response and survival. Dual immunotherapy (IT) combining anti-CTLA-4 and anti-PD1 is increasingly used in these patients as it can allow for long-term control which may lead to treatment discontinuation. However, little data is available regarding the duration of response after IT discontinuation, the subsequent evolution of brain metastases, factors associated with intracranial relapse, response to second-line treatments in case of relapse, and overall survival. Our objective was to collect corresponding data in a real-life setting using the French national database MELBASE.Patients and methods: this national retrospective real-life study included 106 MELBASE patients with MBM treated with dual IT who discontinued IT after disease control. The following data were analyzed: patient and disease characteristics at introduction of dual IT, intracranial relapse rate after discontinuation (primary endpoint), profile of non-relapsing vs relapsing patients, overall relapse rate, response to second line treatment in case of intracranial relapse, factors associated with intracranial relapse, overall survival (OS), progression-free survival (PFS), and treatment-free survival.Results: the median duration of treatment was 11.3 months (6.4-22.3 months) with a median follow-up of 20.6 months (6.7-30.6 months). The intracranial relapse rate was 41% vs an overall relapse rate of 76%. 48% of intracranial relapsers were controlled (CR, PR or SD) by subsequent treatment including resumption of IT. 2-years OS and PFS were estimated at 56.4% and 38.9% respectively for the entire cohort. The median PFS for group 1 (no brain relapse, n=62) was not reached, while it was 4.4 months (95% CI: 2.9-10.8) for group 2 (brain relapse, n=44). Only the size of brain metastases was statistically associated with the occurrence of intracranial relapse (Cox model).Conclusion: dual IT allows sustained control of melanoma brain metastases, even after IT discontinuation. In case of relapse, second-line treatment, including anti-PD1, can be effective with an overall response rate of 22% and a control rate of 48%.