Phase I study of intraventricular administration of rituximab in patients with recurrent CNS and intraocular lymphoma.
OBJECTIVE
We previously determined that intravenous administration of rituximab results in limited penetration of this agent into the leptomeningeal space. Systemic rituximab does not reduce the risk of CNS relapse or dissemination in patients with large cell lymphoma. We therefore conducted a phase I dose-escalation study of intrathecal rituximab monotherapy in patients with recurrent CNS non-Hodgkin's lymphoma (NHL).


METHODS
The protocol planned nine injections of rituximab (10 mg, 25 mg, or 50 mg dose levels) through an Ommaya reservoir over 5 weeks. The safety profile of intraventricular rituximab was defined in 10 patients.


RESULTS
The maximum tolerated dose was determined to be 25 mg and rapid craniospinal axis distribution was demonstrated. Cytologic responses were detected in six patients; four patients exhibited complete response. Two patients experienced improvement in intraocular NHL and one exhibited resolution of parenchymal NHL. High RNA levels of Pim-2 and FoxP1 in meningeal lymphoma cells were associated with disease refractory to rituximab monotherapy.


CONCLUSIONS
These results suggest that intrathecal rituximab (10 to 25 mg) is feasible and effective in NHL involving the CNS.
Rubenstein
James L
JL
Division of Hematology/Oncology, and the Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA 94143, USA. jamesr@medicine.ucsf.edu
Fridlyand
Jane
J
Abrey
Lauren
L
Shen
Arthur
A
Karch
Jon
J
Wang
Endi
E
Issa
Samar
S
Damon
Lloyd
L
Prados
Michael
M
McDermott
Michael
M
O'Brien
Joan
J
Haqq
Chris
C
Shuman
Marc
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D058846:Antibodies, Monoclonal, Murine-Derived; D016543:Central Nervous System Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005134:Eye Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D000069283:Rituximab; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab