Radioimmunotherapy strategies for non-Hodgkin's lymphomas

Radioimmunotherapy offers an exciting new therapeutic modality for patients with relapsed non-Hodgkin's lymphoma; however, considerable debate exists regarding the optimal dose and administration schedule for radioimmunoconjugates. Myelosuppression has been the dose-limiting toxicity of most clinical trials employing radiolabeled antibodies, and this complication has generated both high-dose and low-dose treatment strategies. 'Low-dose' strategies are nonmyeloablative and rely upon repetitive infusions to effectively eradicate tumor masses. Trials incorporating low-dose radioimmunotherapy have documented high response rates, though the durability of these responses remains unclear. The most encouraging nonmyeloablative studies have documented objective responses in 70%-80% of patients, complete responses in 30%-50% of patients, minimal toxicity, and a median response duration of 12 months. In contrast, high-dose trials performed in conjunction with autologous hematopoietic stem cell transplantation have demonstrated objective responses in 95% of patients, complete responses in 85% of patients, with a progression-free survival of 62% and an overall survival of 93% with a median follow-up of two years. Toxicities are considerably higher than those reported with nonmyeloablative regimens, but are modest compared to conventional marrow transplant conditioning regimens incorporating total body irradiation (TBI). Ongoing trials integrating high-dose radioimmuotherapy with high-dose chemotherapy in an autologous transplantation setting are testing the hypothesis that targeted radiotherapy plus chemotherapy will provide increased efficacy and diminished toxicity as compared to nonspecific external beam TBI-containing regimens.