The role of radiolabeled antibodies in the treatment of non-Hodgkin's lymphoma: the coming of age of radioimmunotherapy

This review summarizes the current clinical status of radioimmunotherapy (RAIT) in the treatment of patients with non-Hodgkin's lymphoma (NHL), as a prototype of the advances of RAIT in the management of cancer. Four radiolabeled antibody products are progressing towards commercialization for the RAIT of NHL: I-131-tositumomab (Bexxar (TM)), Y-90-ibritumomab tiuxetan, Y-90-epratuzumab (hLL2), and I-131-Lym-1. All except epratuzumab are murine monoclonal antibodies (Mabs) labeled with an isotope, except that ibritumomab (Zevalin (TM)) adds chimeric rituximab to the product, whereas epratuzumab is solely a humanized Mab. Bexxar and Zevalin target CD20, epratuzumab binds to CD22, and Lym-1 reacts with HLA-DR. Clinical studies have shown that all four antibody products can be safe and efficacious. Bexxar has been shown to induce responses that are relatively better than the prior chemotherapy, and has also been shown to be effective in combination with chemotherapy as a frontline therapy of low-grade and transformed NHL. However, since it is a fully murine Mab, it did show a similar to 60% HAMA rate in untreated patients. Zevalin has been found to be more effective than rituximab, its naked chimeric Mab counterpart, as well as in chemotherapy-relapsed low-grade NHL patients. Both radiolabeled epratuzumab and Lym-1 have shown efficacy in patients who have failed chemotherapy, either with low-grade or aggressive forms of NHL. It appears that Bexxar and Zevalin will be the first two radiolabeled antibodies that may be available for widespread use in the U.S., and will mark the final introduction of RAIT as an approved cancer treatment modality. Future studies will help define the role of these RAIT products in the management of NHL, especially as part of a multimodal therapy of this disease. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.