Intrathecal anti-PD-1 treatment in patients with metastatic melanoma (MM) with leptomeningeal disease (LMD): Real-world data and evidence

e21516 Background: LMD is one of the most severe complications of melanoma and has an extremely poor prognosis. Over the past decade, the incidence of LMD is increasing with improved treatment strategies and prolonged survival. This real-world study aims to evaluate the safety and efficacy of intrathecal anti-PD-1 treatment in MM patients with LMD. Methods: MM patients with LMD diagnosed by MRI and/or cerebrospinal fluid (CSF) cytology were assigned to intrathecal nivolumab infusion 20mg once every 2 weeks (n = 4) or pembrolizumab 20mg once every 3 weeks (n = 3). The patients received a median of 4 cycles of treatment (range 2–7 cycles). Efficacy and safety analyses were performed on all the treated patients. Results: Between June 2022 and December 2022, 7 patients were treated, including 3 cutaneous, 2 acral and 2 primary leptomeningeal melanoma. All patients presented linear or small nodular enhancement of leptomeningeal on MRI. Four patients had concurrent parenchymal brain metastases. The tumor cells were found in 5 patients by CSF cytology, and pathologic diagnosis was obtained by leptomeningeal biopsy in 2 patients. According to RANO-LM criteria, 4 patients responded to treatment with symptom improvement and reduction or disappearance of linear enhancement on MRI, while 3 patients developed progressive disease. The median overall survival (OS) was 39.7 months after initial diagnosis and 24 weeks after LMD. With a median follow-up of 13.3 weeks (range 9.4–20.3 weeks), the median intracranial progression-free survival (IPFS) and median OS for intrathecal anti-PD-1 were 16.1 and 20.3 weeks, respectively. All treatment-related adverse events were grade 1-2, including headache (grade 1, n = 1; grade 2, n = 2) and low back pain (grade 1, n = 1). Conclusions: In this real-world study, intrathecal anti-PD-1 treatment was found to be well tolerated and effective in metastatic melanoma patients with LMD.