Interindividual variability of response to rituximab: from biological origins to individualized therapies.

Abstract

Rituximab has markedly changed the treatment of B-cell malignancies. Despite its widespread use, however, its precise mode of action and the impact of host- and tumor-related factors on rituximab-activated biological pathways were only recently clarified. Biological mechanisms resulting in complete resistance to rituximab may exist at both the cellular and subcellular level; however, their frequency and their impact on clinical response are unclear. The identification of Fcγ receptor polymorphisms that can influence anti-CD20 antibody activity has resulted in the development of third-generation anti-CD20 antibodies. However, it is also now appreciated that pharmacokinetic variability is a major factor affecting clinical response to anti-CD20 antibodies. The concept of antigenic mass, which takes into account the total tumor load and the expression levels of the target antigen CD20, is able to explain the correlation between rituximab plasma concentrations and treatment responses. Thus, it can be hypothesized that dosing regimens that take this information into account will help to improve response rates.

• Authors: Guillaume Cartron, Ralf Ulrich Trappe, Philippe Solal-Céligny, Michael Hallek
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 17 Issue 1 Pg. 19-30 (Jan 01 2011) ISSN: 1557-3265 [Electronic] United States
• PMID: 21208903 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: ©2011 AACR.

Chemical References

• Antibodies
• Antibodies, Monoclonal, Murine-Derived
• Antigens, CD20
• Rituximab

Topics

• Antibodies (immunology)
• Antibodies, Monoclonal, Murine-Derived (blood, immunology, therapeutic use)
• Antigens, CD20 (immunology)
• Humans
• Lymphoma, B-Cell (drug therapy, immunology)
• Models, Immunological
• Precision Medicine
• Rituximab