Melanoma brain metastases outcomes following nivolumab and relatlimab after ipilimumab and nivolumab progression.

Purpose: Relatlimab (rela) with nivolumab (nivo) has demonstrated durable responses in pre-treated advanced melanoma. Intracranial responses have been demonstrated with the combination of ipilimumab (ipi) with nivo in melanoma brain metastases (MBM). We sought to characterize intracranial outcomes in patients treated with nivo/rela following ipi/nivo. Patients and Methods: A retrospective analysis of patients who received nivo/rela with MBM was performed. Patients had prior ipi/nivo and active MBM. The primary endpoint was central nervous system progression free survival (CNS-PFS). Secondary endpoints included overall survival (OS), extracranial-PFS, and safety with local therapy. Results: We identified 24 patients, with a median follow-up of 14.2-months. Median age was 72 (range 31–85), 75% were male, and 29% had neurologic symptoms. The median total prior lines of systemic therapy was 3 (range: 1–8), and in the metastatic setting 2 (range: 1–8). Eighteen (75%) patients received local therapy with nivo/rela, 16 (67%) stereotactic radiosurgery (SRS), 2 (8%) whole brain radiation therapy, and 3 (13%) surgery. Median CNS-PFS was 5.3 months (95% CI 2.5–24.2) and median extracranial-PFS was 2.8 months (95% CI 1.9–15.7). Median OS was 12.1 months (95% CI 5.3–24.2), with a 12-month rate of 55%. No patients developed symptomatic radiation necrosis following SRS. Conclusion: Nivo/rela demonstrates moderate efficacy for MBM after ipi/nivo. Concurrent local therapy appears safe alongside nivo/rela.