New Drug Alert

Abstract

Ibritumomab tiuxetan (Zevalin) is the first radioimmunoconjugate to receive FDA approval for the treatment of cancer. The drug is indicated for the treatment of relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma (NHL), including patients with follicular NHL refractory to rituximab. Zevalin is a murine monoclonal antibody (the murine parent of rituximab) linked to the radioisotope yttrium-90, targeting the CD20 antigen on the surface of mature B cells and B-cell tumors, inducing cellular damage in both the target and neighboring cells. Zevalin was approved based on two major studies conducted in the United States. The Zevalin regimen includes rituximab given first, followed seven to 10 days later by a second infusion prior to Zevalin. The first study, on which full FDA approval was based, included 54 patients with relapsed follicular lymphoma who no longer had an adequate response to rituximab. Of this group 74 percent of patients responded to treatment with Zevalin as part of the therapeutic regimen, including 15 percent who achieved a complete response. The second study, on which accelerated FDA approval was based, was a Phase III randomized, controlled trial conducted in 143 patients with relapsed or refractory low-grade or follicular NHL or transformed B-cell NHL. Among patients who were randomized to receive Zevalin as part of the therapeutic regimen, the overall response rate was 80 percent versus 56 percent in patients who received rituximab alone. Thirty percent in the Zevalin-treated group achieved a confirmed complete remission versus 16% of rituximab-treated patients. Two experts experienced with ibritumomab were asked what advice they would have for clinicians starting to use the agent. Russell Schilder, MD, is a member of the Department of Medical Oncology at Fox Chase Cancer Center in Philadelphia; and Leo I. Gordon, MD, is the Abby and John Friend Professor of Cancer Research, Professor of Medicine, and Chief of the Division of Hematology/Oncology at Northwestern University Feinberg School of Medicine in Chicago.