Mark S. Kaminski, MD

Tositumomab/iodine-131 tositumomab (Bexxar) and ibritumomab tiuxetan (Zevalin) are radioimmunoconjugates targeting the CD20 antigen. Both agents are approved in the United States for use in relapsed or refractory, indolent or transformed, B-cell lymphoma. These agents are well tolerated and have the highest levels of single-agent activity observed in these histologies. This review will summarize the key trials that led to approval of both I-131 tositumomab and ibritumomab tiuxetan, and then focus on four novel therapeutic concepts in radioimmunotherapy: retreatment, therapy of de novo indolent lymphoma, therapy of aggressive histologies, and incorporation in high-dose therapy programs utilizing autologous stem cell support.

Despite the remarkable resultsso ably described by Ghobrialand Witzig in this issue ofONCOLOGY, radioimmunotherapyfor low-grade and transformed lowgradelymphoma is a treatment thatappears to be currently underutilizedby clinicians. The two US Food andDrug Administration (FDA)-approvedanti-CD20 radiolabeled antibodies,Y-90 ibritumomab tiuxetan (Zevalin)and tositumomab/iodine-131 (I-131)tositumomab (Bexxar), have producedresponse rates from 50% to 80% andcomplete response rates from 20% to40% in studies of patients with varyingresistance to chemotherapy as wellas rituximab (Rituxan), making theseagents probably the most active systemicagents we have available forlow-grade B-cell lymphoma.

At first glance, the concept of using radionuclide-labeled monoclonal antibodies to target radioactivity to tumor sites for the detection and possible treatment of malignancies appears quite appealing in terms of its rationale and simplicity. However, as is apparent in Dr. Divgi's comprehensive review of the many clinical studies that have been performed to test this concept, there are a number of complexities that require further study and resolution so that this approach can be optimally and more widely applied in clinical medicine. Although Dr. Divgi touches on many of these issues, some points are worthy of emphasis and further discussion.