Real-world outcomes in patients with brain metastases secondary to melanoma treated with nivolumab/relatlimab.

Abstract

e14001 Background: Patients with melanoma brain metastases (MBM) have a poor prognosis. Immune checkpoint inhibitors (ICI) have improved the prognosis of patients with MBM. The combination of anti-PD1 (nivolumab, nivo) and anti-cytotoxic T-lymphocyte antigen-4 (ipilimumab, ipi) has demonstrated the highest intracranial and extracranial response rates and durability. Combination ipilimumab / nivolumab (ipi/nivo) is the standard first line (1L) therapy for patients with MBM. Data pertaining to the efficacy of the alternative, more tolerable, front-line regimen of nivolumab/relatlimab (nivo/rela) is lacking. Methods: We performed a retrospective cohort study of patients with MBM treated with nivo-rela from May 2022 to December 2023. Information pertaining to patient demographics, timing of therapy (radiation, nivo-rela), response rates and adverse effects were collected. The intracranial response was categorized as an increase, stable, or decrease in brain lesion size. Extracranial response was defined as durable clinical benefit (stable disease (SD), partial response (PR), or complete response (CR)) sustained for 6 months. Progression free survival and overall survival was calculated. Results: A total of 44 patients were identified with a median follow-up of 25 months. The majority of patients were male (28 of 44 [63.6%]), with a median age of 69 years (range 31-87 years). Most patients were BRAFV600 mutated (29 of 44 [65.9%]). The median time from primary melanoma diagnosis to the development of MBM was 34 months (range 0 - 644 months). The median interval between MBM diagnosis and the initiation of nivo-rela was 8.6 months (range -21-94 months) with 6 (13.6%) treated in the 1L setting, 16 (36.4%) treated in 2L, and 22 (50%) in the ≥3L and beyond. Thirty-nine patients had brain metastasis at the time of nivo-rela initiation. Most patients (30 of 44 [68.2%]) had 1-3 MBM, while (14 of 44 [31.8%]) had more than 3 MBM. Two patients had leptomeningeal disease. (33 of 44 [75.0%]) received local intracranial stereotactic radiotherapy (SRT). The estimated survival rates were 77% (95% CI: 62% to 87%) at one year and 67% (95% CI: 50% to 80%) at two years following MBM diagnosis. We saw an intracranial clinical benefit (decreasing and stable) in (20 of 44 [45.5%]) patients. For extracranial response, we saw durable clinical benefit in (17 of 44 [38.6%]) patients. Conclusions: The combination of nivo-rela showed intracranial activity in patients with MBM, particularly in the 1L. Prospective trials are needed to confirm these findings and provide data on the optimal use of systemic and local therapies in this challenging patient population. Patient demographics. N Mean S.D. Min Median Max % Months from Prim. Dx to BM Dx 44 62.2 101.6 0.0 34.1 643.7 Months after BM to start Nivo-Rela 44 15.0 20.9 -20.7 8.6 94.3 Age at BM diagnosis 44 66.9 11.2 31.0 69.0 87.0 Female 16 36.4 Male 28 63.6 1-3 MBM 30 68.2 3+ MBM 14 31.8