ArticleClinical cancer research : an official journal of the American Association for Cancer Research2014
Complement activation and intraventricular rituximab distribution in recurrent central nervous system lymphoma.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- The pharmacokinetics and its covariates of rituximab in different clinical populations: a systematic review and narrative synthesis.European journal of clinical pharmacology · 2026Pooled it
- A phase II study of radioimmunotherapy with intraventricularPediatric blood & cancer · 2018Trial
- Methodologies for Population Pharmacokinetic Modeling of Target-Site Drug Exposure: A Narrative Review of Current Strategies.Clinical pharmacokinetics · 2026Review
- Intrathecal administration of Anti-Nogo-A antibody in macaque monkeys: Pharmacokinetics, tissue penetration and target interaction.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- Article
- Primary Central Nervous System Lymphoma: Long-Term Treatment Outcomes and Cost-Analysis from a Retrospective Study of High-Dose Methotrexate Based Chemoimmunotherapy and Reduced Dose Radiation Therapy Approach.Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion · 2022Article
- Review
- Review
- The Cerebroventricular Environment Modifies CAR T Cells for Potent Activity against Both Central Nervous System and Systemic Lymphoma.Cancer immunology research · 2021Article
- No Early Effect of Intrathecal Rituximab in Progressive Multiple Sclerosis (EFFRITE Clinical Trial).Multiple sclerosis international · 2021Article
- Modulation of the Complement System by Neoplastic Disease of the Central Nervous System.Frontiers in immunology · 2021Review
- On point in primary CNS lymphoma.Hematological oncology · 2020Review
- Molecular profiling of primary central nervous system lymphomas - predictive and prognostic value?Current opinion in neurology · 2019Review
- Phase 1 investigation of lenalidomide/rituximab plus outcomes of lenalidomide maintenance in relapsed CNS lymphoma.Blood advances · 2018Article
- Estimation of intrathecal IgG synthesis: simulation of the risk of underestimation.Annals of clinical and translational neurology · 2018Article
- Biology of CNS lymphoma and the potential of novel agents.Hematology. American Society of Hematology. Education Program · 2017Review
- The Challenge of Primary Central Nervous System Lymphoma.Hematology/oncology clinics of North America · 2016Review
- New approaches in primary central nervous system lymphoma.Chinese clinical oncology · 2015Review
- Phosphodiesterase type 5 inhibitor Tadalafil increases Rituximab treatment efficacy in a mouse brain lymphoma model.Journal of neuro-oncology · 2015Article
- Progress in central nervous system lymphomas.British journal of haematology · 2014Review
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
purposeTo elucidate the mechanistic basis for efficacy of intrathecal rituximab. We evaluated complement activation as well as the pharmacokinetics of intraventricular rituximab in patients who participated in two phase 1 multicenter studies. EXPERIMENTAL
designWe evaluated complement activation as a candidate mediator of rituximab within the central nervous system (CNS). Complement C3 and C5b-9 were quantified by ELISA in serial cerebrospinal fluid (CSF) specimens after intraventricular rituximab administration. We determined rituximab concentration profiles in CSF and serum. A population three- compartment pharmacokinetic model was built to describe the disposition of rituximab following intraventricular administration. The model was derived from results of the first trial and validated with results of the second trial.
resultsComplement C3 and C5b-9 were reproducibly activated in CSF after intraventricular rituximab. Ectopic expression of C3 mRNA and protein within CNS lymphoma lesions was localized to myeloid cells. Constitutive high C3 activation at baseline was associated with adverse prognosis. A pharmacokinetic model was built, which contains three distinct compartments, to describe the distribution of rituximab within the neuroaxis after intraventricular administration.
conclusionsWe provide the first evidence of C3 activation within the neuroaxis with intraventricular immunotherapy and suggest that complement may contribute to immunotherapeutic responses of rituximab in CNS lymphoma. Penetration of rituximab into neural tissue is supported by this pharmacokinetic model and may contribute to efficacy. These findings have general implications for intraventricular immunotherapy. Our data highlight potential innovations to improve efficacy of intraventricular immunotherapy both via modulation of the innate immune response as well as innovations in drug delivery.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.