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:
131I-tositumomab (
Bexxar), 90Y-ibritumomab tiuxetan, 90Y-epratuzumab (
hLL2), and 131I-Lym-1. All except
epratuzumab are murine
monoclonal antibodies (Mabs) labeled with an
isotope, except that ibritumomab (
Zevalin) 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 approximately 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.