Cerebrospinal Fluid Penetrance of Daratumumab in Leptomeningeal Multiple Myeloma

To the editor: Central nervous system (CNS) involvement in multiple myeloma (MM) is a rare manifestation of extramedullary disease with an incidence of approximately 1%, which is characterized by the presence of leptomeningeal disease, or less frequently, solitary or multiple intraparenchymal plasmacytomas. CNS disease is more common in patients with advanced MM. Patients with highrisk cytogenetics, high levels of circulating MM cells and extramedullary disease at initial diagnosis, have an increased risk of developing CNS MM. The outcome is very poor with an overall survival ranging from 2 to 7 months from the detection of CNS involvement. To date, there is no standard treatment for CNS MM. Patients are frequently treated with intrathecal therapy and irradiation, but evidence supporting their efficacy is limited and only obtained from case reports and small case series. Importantly, the majority of systemically administered anti-MMagents do not substantially cross the blood brain barrier (BBB), which protects the CNS from a multitude of drugs as well as circulating pathogens. However, several studies have shown that the immunomodulatory drugs (IMiDs) thalidomide and pomalidomide, as well as the novel proteasome inhibitor marizomib, can be detected in cerebrospinal fluid (CSF) after systemic administration. To the best of our knowledge, no data is currently available on the ability of CD38-targeting monoclonal antibodies, such as daratumumab, to cross the BBB. To improve our understanding of the BBB penetration properties of daratumumab, as well as intrathecal M-protein production, we measured the concentration of daratumumab and M-protein in serum and CSF in a patient who presented with CNS MM