Immunotherapy for leptomeningeal disease from solid tumors: current clinical outcomes and future opportunities

Abstract

Leptomeningeal disease is a debilitating, late-stage form of metastatic cancer disseminated within the cerebrospinal fluid, subarachnoid space, and leptomeninges, leading to significant neurological morbidity and mortality. As systemic cancer treatments improve, rates of leptomeningeal disease have increased, yet prognosis remains exceedingly poor. A wide range of treatment modalities have been trialed; however, no standard of care has been established. Additionally, many clinical trials exclude patients with leptomeningeal disease, limiting available prospective data. In this review, we discuss the efficacy of immunotherapy for leptomeningeal disease from solid tumors including systemic and intrathecal therapies, as well as combined therapy regimens. Our review indicates a continued deficiency in the current prospective literature and highlights ongoing research regarding the leptomeningeal immune microenvironment, which will be critical in directing future study of leptomeningeal disease treatment. Currently, the efficacy of immunotherapies on leptomeningeal disease appears limited, and further prospective research is needed to draw significant conclusions. However, recent advancement in understanding the leptomeningeal microenvironment points to potential efficacy of novel immunotherapies targeting the innate immune system, and further study is warranted to evaluate the efficacy of these treatments in this subpopulation of patients.