Radioimmunotherapy of relapsed non-Hodgkin's lymphoma with Zevalin, a Y-90-labeled anti-CD20 monoclonal antibody

Approximately 55,400 new cases of non-Hodgkin's lymphoma (NHL) are diagnose d each year, with the overall prevalence of the disease now estimated to be 243,000. Until recently, treatment alternatives for advanced disease inclu ded chemotherapy with or without external beam radiation. Based on the resu lts of several clinical trials, the chimeric monoclonal antibody Rituximab has now been approved by the United States Food and Drug Administration as a treatment for patients with relapsed or refractory, low-grade or follicul ar, B-cell NHL. Several other monoclonal antibodies in conjugated and uncon jugated forms have been evaluated in the treatment of MIL. Ibritumomab, the murine counterpart to Rituximab, radiolabeled with Y-90 (Zevalin), is pres ently being evaluated in clinical trials. The success of radioimmunotherapy is dependent upon the appropriate choice of antibody, isotope, and chelato r-linker. The Ibritumomab antibody targets the CD20 antigen. The antibody i s covalently bound to the chelator-linker tiuxetan (MX-DTPA), which tightly chelates the isotope Y-90. To date, two Phase I/II Zevalin clinical trials have been completed in patients with low-grade, intermediate-grade, and ma ntle cell NHL. The overall response rate was 64% in the first trial and 67% in the later trial. Phase II and III trials are ongoing.