Intraventricular Rituximab Safe in Recurrent CNS Lymphoma

By David Douglas

NEW YORK APR 24, 2007 (Reuters Health) - Initial data indicate that intraventricular administration of rituximab is a useful approach in patients with recurrent CNS and intraocular non-Hodgkin"s lymphoma (NHL), researchers report in the April 10th issue of the Journal of Clinical Oncology.

"We have obtained preliminary safety and efficacy data in this first phase I study of intraventricular administration of a naked monoclonal antibody," lead investigator Dr. James L. Rubenstein told Reuters Health. "We are also using this study, as well as its successor, to gain insights into mechanisms of resistance to rituximab."

Dr. Rubenstein of the University of California, San Francisco and colleagues previously determined that intravenous administration of rituximab results in limited penetration into the leptomeningeal space. Moreover, systemic rituximab does not reduce the risk of CNS relapse or dissemination in patients with large cell lymphoma.

To evaluate an intraventricular approach, the researchers conducted a dose-escalation study of intrathecal rituximab monotherapy in 10 patients with recurrent NHL. Doses ranged from 10 to 50 mg.

The maximum tolerated dose was determined to be 25 mg and rapid craniospinal axis distribution was seen. Cytologic responses were detected in 6 patients and 4 showed a complete response. Two patients had improvement in intraocular NHL and one had resolution of parenchymal NHL.

The team also found that high RNA levels of Pim-2 and FoxP1 in meningeal lymphoma cells were associated with rituximab-refractory disease.

These results, the investigators conclude, "constitute the basis for a successor trial to examine the safety, pharmacokinetics, and efficacy of intra-CSF injection of rituximab plus methotrexate in the treatment of recurrent CNS and ocular lymphomas."

"The rationale for this approach," they add, "is underscored by the increasing body of evidence that suggests that rituximab may sensitize malignant or autoimmune B cells to apoptosis induced by genotoxic therapy."

SOURCE:

• J Clin Oncol 2007;25:1350-1356.