Phase I Study of Intraventricular Administration of Rituximab in Patients With Recurrent CNS and Intraocular Lymphoma
Open accessAbstract
Purpose: 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). Patients and 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. Conclusion: These results suggest that intrathecal rituximab (10 to 25 mg) is feasible and effective in NHL involving the CNS.
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Direct CNS administration is limited by diffusion distance and rapid efflux of drugs out of the CNS within hours.
“However, direct CNS administration is invasive, which may cause infection and tissue damage, and is also limited by diffusion distance and rapid efflux of drugs out of the CNS within hours (8–10).”
From Neurotransmitter-derived lipidoids (NT-lipidoids) for enhanced brain delivery through intravenous injection (2020) · cites this paper as [9]
The CSF Rituximab Concentration Profiles section (page unavailable) reports a rapid decline in CSF concentration after dosing. The pharmacokinetic results (page unavailable) distinguish a 2–3-hour initial distribution half-life from a 13.5–34.9-hour elimination half-life. The paper does not identify diffusion distance as a limitation or establish that drugs leave the CNS within hours. (LLM, conf=0.84)
Experimental — accuracy not yet measuredDirect CNS administration is invasive and may cause infection and tissue damage.
“However, direct CNS administration is invasive, which may cause infection and tissue damage, and is also limited by diffusion distance and rapid efflux of drugs out of the CNS within hours (8–10).”
From Neurotransmitter-derived lipidoids (NT-lipidoids) for enhanced brain delivery through intravenous injection (2020) · cites this paper as [9]
The Study Design describes direct CNS delivery through an Ommaya reservoir and by lumbar puncture, supporting the characterization of the procedure as invasive. The adverse-events section reports possible leukoencephalopathy, but does not attribute it to the invasive procedure; the passages found do not identify infection or procedure-caused tissue damage as risks. (LLM, conf=0.82)
Experimental — accuracy not yet measured
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Cites
Smyth, G. K. (2004) · Statistical Applications in Genetics and Molecular Biology · doi:10.2202/1544-6115.1027 · Cited by 11,829 · see citing works
Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis
Edwards, J. C. W., Szczepański, L., Szechiński, J., Filipowicz-Sosnowska, A., Emery, P., Close, D. R., Stevens, R. M., & Shaw, T. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa032534 · Cited by 2,623 · see citing works
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Research works printed but not linked: 1
- Abrey LE, Batchelor TT, Ferreri AJ, et al: Report of an international workshop to standardize baseline evaluation and response criteria for primary CNS lymphoma. J Clin Oncol 23:5034-5043, 2005
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Ma, F., Yang, L., Sun, Z., Chen, J., Rui, X., Glass, Z., & Xu, Q. (2020) · Science Advances · doi:10.1126/sciadv.abb4429 · Cited by 218 · see citing works
- Authors
- Rubenstein, J. L., Fridlyand, J., Abrey, L., Shen, A., Karch, J., Wang, E., Issa, S., Damon, L., Prados, M., McDermott, M., O'Brien, J., Haqq, C., & Shuman, M.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- From the Division of Hematology/Oncology, and the Departments of Epidemiology and Biostatistics, Pathology, Neurological Surgery, and Division of Ocular Oncology, University of California, San Francisco, San Francisco, CA; and Memorial Sloan-Kettering Cancer Center, New York, NY
- ORCID
- Venue
- Journal of Clinical Oncology
- Published
- 2007-04-10
- Volume
- 25
- Issue
- 11
- Pages
- 1350-1356
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- OpenAlex
- W2145727048
- Cited by
- 327
- References
- 2
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 9 · 2023: 9 · 2022: 14 · 2021: 17 · 2020: 16 · 2019: 13 · 2018: 16 · 2017: 14 · 2016: 23 · 2015: 18 · 2014: 19 · 2013: 24 · 2012: 25
- FWCI
- 18.06
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Oncology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Mount Zion Health Fund
- National Institutes of Health (5m01rr000079-42)
- University of California, San Francisco (P50CA097257)
- National Cancer Institute (CA097257, R01CA101042, P50CA097257)
- National Center for Research Resources (M01 RR-00079)
- Topics
- Health Sciences › Medicine › Neurology › CNS Lymphoma Diagnosis and Treatment
- Health Sciences › Medicine › Pathology and Forensic Medicine › Lymphoma Diagnosis and Treatment
- Health Sciences › Medicine › Genetics › Chronic Lymphocytic Leukemia Research
- Keywords
- rituximab, intraventricular administration, intrathecal chemotherapy, intraocular lymphoma, non-Hodgkin lymphoma, Ommaya reservoir, maximum tolerated dose, PIM2, FOXP1, meningeal lymphoma, central nervous system relapse
- MeSH terms
- Rituximab, Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Dose-Response Relationship, Drug, Enzyme-Linked Immunosorbent Assay, Eye Neoplasms, Female, Humans, Lymphoma, Non-Hodgkin, Male, Middle Aged, Neoplasm Recurrence, Local, Central Nervous System Neoplasms, Treatment Outcome, Antibodies, Monoclonal, Murine-Derived
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