Intraventricular application of rituximab as a treatment option in patients with CNS lymphoma and leptomeningeal disease

Abstract

1521 Background: Most patients (pts) with primary central nervous system lymphoma (PCNSL) relapse after initial response to treatment, often presenting with leptomeningeal disease. Since the majority of PCNSL are B-cell neoplasms expressing the CD20 surface antigen treatment with the chimeric monoclonal antibody (Mab) rituximab might be reasonable. The primary objective was to evaluate feasibility and safety of direct administration of the anti-CD20 antibody into the cerebro spinal fluid (CSF). Methods: Pts with intracranial lesions and/or leptomeningeal involvement of B-cell neoplasms expressing the CD20 surface antigen were included. In order to define the tolerated single dose, injections of 10–40 mg rituximab in a volume of 1–4 ml were administered over two minutes via an ommaya reservoir (n=4) or intrathecally (n=2). Drug clearance from the CSF was determined by measuring rituximab levels in the CSF and blood by ELISA. Results: Treatment with rituximab at single dosis of up to 35mg thrice weekly was safe and well tolerated in 5/6 pts. Acute neurotoxicity in one pt (PN6) was probably related to a high tumor cell burden in the CSF and a rapid tumor cell lysis after intrathecal rituximab. Measurement of rituximab concentrations in the CSF showed severalfold higher values after intraventricular administration compared to those after intravenous rituximab application. Clearing of tumor cells in the CSF and a complete remission of leptomeningeal lymphoma manifestation was achieved in four pts. However, there was no effect of rituximab on parenchymal lymphoma. Conclusions: Taken together, these data suggest that direct administration of rituximab into the CSF may have a role in the treatment of leptomeningeal disease in pts with CNS lymphoma. However, the therapeutic value of systemic treatment with the antibody remains questionable. To better define the value of rituximab treatment in CNS lymphoma with lymphomatous meningitis, future studies should investigate dose intensification as well as combination with other chemotherapeutic drugs or radiotherapy. No significant financial relationships to disclose.