Radioimmunotherapy for non-Hodgkin's lymphomas: a historical perspective

One of the most promising therapeutic approaches currently under investigation for low-grade non-Hodgkin's lymphoma is the administration of monoclonal antibodies that recognize tumor-associated antigens. These antibodies can be used either in unmodified form or conjugated to cytotoxic drugs, toxins, or radionuclides. To date, the most promising of the immunoconjugates are radiolabeled antibodies. Radioimmunotherapy is an attractive approach because radiolabeled antibodies are effective even in the face of defective host immune effector function, antigen-negative variants, and poor penetration of the antibody into tumors. Iodine-131-and Yttrium-90-conjugated antibodies have shown superior response rates compared with unconjugated antibodies and have produced complete responses in 15% to 40% of treated patients. A variety of treatment approaches are currently being investigated, including administering radiolabeled antibodies in combination with chemotherapy and administering myeloablative doses with stem-cell rescue. This latter strategy has yielded complete remissions in the majority of treated patients, some durable for more than 5 years.