Melanoma leptomeningeal disease: Advances in diagnosis and emerging therapeutic strategies
Year: 2026
Type: article
Abstract: Melanoma leptomeningeal disease (LMD) is a rare and severe manifestation of advanced melanoma involving malignant infiltration of the leptomeninges and cerebrospinal fluid. Historically, survival was measured in weeks, but recent advances in diagnostics and therapy have begun to improve outcomes. This narrative review summarizes current evidence on the epidemiology, biology, diagnosis, and management of melanoma LMD, with emphasis on studies from the past five years. Emerging cerebrospinal fluid liquid biopsy methods, including circulating tumor cell and cell free DNA analysis, allow earlier detection, identification of actionable mutations, and real time monitoring of disease activity. Modern systemic therapies have extended median overall survival to approximately 8.4 months compared with historical outcomes of 2.9 months to 3.7 months. Immune checkpoint inhibitors and B-rapidly accelerated fibrosarcoma and mitogen-activated protein kinase targeted therapies both contribute to these improvements, and early studies of intrathecal immunotherapy show encouraging clinical activity. Additional innovations such as proton craniospinal irradiation and novel drug delivery strategies reflect an evolving treatment landscape. Continued progress will depend on dedicated clinical trials, broader inclusion of patients with LMD, and deeper understanding of the leptomeningeal immune microenvironment.
Authors: Michael L Middleton, Brandon Lucke-Wold
Institution: University of Florida
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7135369786