Rituximab: mechanism of action.

Primary CNS lymphoma (PCNSL) is a rare form of extranodal non-Hodgkin lymphoma that is typically confined to the brain, eyes, and cerebrospinal fluid without evidence of systemic spread. The prognosis of patients with PCNSL has improved during the last decades with the introduction of high-dose methotrexate. However, despite recent progress, results after treatment are durable in half of patients, and therapy can be associated with late neurotoxicity. PCNSL is an uncommon tumor, and only four randomized trials and one phase III trial have been completed so far, all in the first-line setting. To our knowledge, no randomized trial has been conducted for recurrent/refractory disease, leaving many questions unanswered about optimal first-line and salvage treatments. This review will give an overview of the presentation, evaluation, and treatment of immunocompetent patients with PCNSL.

Primary CNS Lymphoma

CNS events in elderly patients with aggressive lymphoma treated with modern chemotherapy (CHOP-14) with or without rituximab: an analysis of patients treated in the RICOVER-60 trial of the German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL).

This case is submitted by Drs. Francisco J. Ascaso, Maria Rojo, and Enrique Minguez from the Department of Ophthalmology, “Lozano Blesa” University Clinic Hospital, Zaragoza, Spain, for the Diagnostic and Therapeutic Challenges Section of Retina; and commented by Dr. Steven M. Cohen, Clearwater, Flo

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Diagnostic and therapeutic challenges.

The brain develops and functions within a strictly controlled environment resulting from the coordinated action of different cellular interfaces located between the blood and the extracellular flui...

Physiology of blood-brain interfaces in relation to brain disposition of small compounds and macromolecules.

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 lymp...

https://ascopubs.org/doi/pdf/10.1200/JCO.2006.09.7311

Endi Wang

Papers

Phase I Study of Intraventricular Administration of Rituximab in Patients With Recurrent CNS and Intraocular Lymphoma