Submitted November 12, 2008
Accepted January 18, 2009
A re-examination of radioimmunotherapy in the treatment of non-Hodgkin lymphoma: Prospects for dual-targeted antibody/radioantibody therapy
Robert M. Sharkey*, Oliver W. Press, and David M. Goldenberg
Garden State Cancer Center, Center for Molecular Medicine and Immunology, Belleville, NJ, United States
Fred Hutchinson Cancer Research Center and University of Washington, Seattle, WA, United States
* Corresponding author; email: rmsharkey{at}gscancer.org.
Antibody-based therapies, both unconjugated antibodies and radioimmunotherapy, have had a significant impact on the treatment of non-Hodgkin lymphoma. Single-agent rituximab is an effective therapy, but it is being increasingly used with combination chemotherapy to improve the objective response and its duration. The approved anti-CD20 radioimmunoconjugates (90Y-ibritumomab tiuxetan or 131I-tositumomab) have had encouraging results, with trials now seeking to incorporate a radioimmunoconjugate in various settings. However, new preclinical data raise important questions concerning current radioimmunoconjugate treatment regimens and ways to improve them. In radioconjugate therapy, nearly 900 mg of the unlabeled anti-CD20 IgG antibody is pre-dosed to the patient before the anti-CD20 antibody conjugated to either 90yttrium or 131iodine is given. Combining an unconjugated anti-CD20 antibody therapy with a radioimmunoconjugate binding to a non-competing antigen might improve responses by allowing optimal uptake of each agent. Preclinical models have indicated that careful consideration should be given to pre-dosing when using competing antibodies, but that consolidation anti-CD20 therapy enhances the efficacy of radioimmunoconjugate therapy. New technologies, such as pretargeted radioimmunotherapy, also hold promise by reducing toxicity without sacrificing efficacy, and consideration should be given to fractionating or giving multiple radioimmunoconjugate treatments. This perspective discusses how these issues could impact current and future clinical trials.
