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Prepublished online as a Blood First Edition Paper on September 5, 2002; DOI 10.1182/blood-2002-06-1636.
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Blood, 15 January 2003, Vol. 101, No. 2, pp. 466-468
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Brief report
Rituximab therapy for CNS lymphomas: targeting the
leptomeningeal compartment
James L. Rubenstein,
Dan Combs,
Jay Rosenberg,
Arthur Levy,
Michael McDermott,
Lloyd Damon,
Robert Ignoffo,
Kenneth Aldape,
Arthur Shen,
Dana Lee,
Antonio Grillo-Lopez, and
Marc A. Shuman
From the Division of Hematology/Oncology,
Comprehensive Cancer Center, Cancer Research Institute, Department of
Neurosurgery, and Department of Pathology, UCSF; San Francisco, CA;
Yale University School of Medicine, New Haven, CT; Genentech, South San
Francisco, CA; and IDEC Pharmaceuticals, San Diego, CA.
Most lymphomas that involve the central nervous system are B-cell
neoplasms that express the cell surface molecule CD20. After intravenous administration, rituximab can be reproducibly measured in
the cerebrospinal fluid (CSF) in patients with primary central nervous
system lymphoma; however, the CSF levels of rituximab are approximately
0.1% of serum levels associated with therapeutic activity in patients
with systemic non-Hodgkin lymphoma. Because lymphomatous meningitis is
a frequent complication of non-Hodgkin lymphoma, we have conducted an
analysis of the safety and pharmacokinetics of direct intrathecal
administration of rituximab using cynomolgus monkeys. No significant
acute or delayed toxicity, neurologic or otherwise, was detected.
Pharmacokinetic analysis suggests that drug clearance from the
CSF is biphasic, with a terminal half-life of 4.96 hours. A phase 1 study to investigate the safety and pharmacokinetics of intrathecal
rituximab in patients with recurrent lymphomatous meningitis will be
implemented based on these findings.
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