Abstract

Radioimmunotherapy (RIT), in which a radionuclide conjugated to an antibody directed towards a tumor associated antigen (the radioimmunoconjugate) is administered in a therapeutic regimen, represents a significant addition to the treatment of non-Hodgkin's lymphoma (NHL). RIT offers several advantages for this heterogenous disease, foremost being the ability to kill tumor cells adjacent to cells to which the radioimmunoconjugate is bound (the cross-fire effect). Thus, RIT is cytotoxic to tumor cells that may be inaccessible to the antibody, or do not express the target antigen in sufficient quantities for antibody binding. The radioimmunoconjugate 90Y-ibritumomab tiuxetan is directed against the B-cell antigen, CD20. Phase II and III clinical trials with this agent report overall response rates of 74% to 83% (complete response rates 15% to 51%) in patients with relapsed or refractory, indolent or transformed NHL, including patients refractory to rituximab. Median durations of response range up to 13.9 months. A variety of RIT approaches are under investigation to improve outcomes in patients with NHL, including the use of radioimmunoconjugates combined with chemotherapy, and myeloablative therapeutic strategies.