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

Purpose Leptomeningeal disease (LMD) is a severe complication of melanoma with a very poor prognosis. Despite improved treatment strategies and prolonged survival, the incidence of LMD has increased over the past decade. This real-world study aims to evaluate the efficacy and safety of intrathecal anti-PD-1 treatment in melanoma patients with LMD. Methods Melanoma patients with LMD diagnosed by magnetic resonance imaging (MRI) and/or cerebrospinal fluid (CSF) cytology were treated with intrathecal infusions of nivolumab 20 mg once every 2 weeks ( n = 5) or pembrolizumab 20 mg once every 3 weeks ( n = 3), alongside systemic therapy. Patients received a median of 5.5 treatment cycles (range 2–9). Efficacy and safety analyses were performed on all treated patients. Results From June 2022 to February 2023, eight patients were treated, including four with cutaneous melanoma, two with acral melanoma, and two with primary leptomeningeal melanoma. All patients exhibited linear or small nodular enhancement of the leptomeninges on MRI. Four patients had concurrent parenchymal brain metastases. Tumor cells were identified in six patients by CSF cytology, and two patients underwent leptomeningeal biopsy for pathological diagnosis. According to the RANO-LM criteria, five patients responded to treatment with symptom improvement and reduction or disappearance of linear enhancement on MRI, while three patients developed progressive disease. With a median follow-up of 20.7 weeks (range 8.1–45.3 weeks), the median OS and median intracranial progression-free survival (IPFS) for intrathecal anti-PD-1 treatment were 21.1 and 16.1 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 demonstrated potential clinical benefits and was well tolerated in metastatic melanoma patients with LMD.