Radioimmunotherapy in follicular lymphoma: some like it hot….

Therapeutic monoclonal antibodies (MoAbs) have been the major breakthrough in the treatment of both indolent and aggressive B-cell non-Hodgkin's lymphoma (NHL), and have become standard of care for these diseases. However, patients may not respond to antibody therapy, or resistance can develop. Radioimmunotherapy (RIT) makes use of continuous low dose radiation emitted by radioisotopes targeted directly to the lymphoma cells. Both the (131)I-labeled murine CD20 MoAb tositumomab (Bexxar®) and (90)Y-labeled ibritumomab-tiuxetan (Zevalin®) have been shown to be more effective than unlabeled MoAbs in terms of overall and complete response rates in follicular lymphoma (FL) patients, and both agents have a high response rate even in rituximab-resistant patients. Long-term responses, especially in complete responders, have been described in up to one third of the patients. In FL patients consolidation with (90)Y-labeled ibritumomab-tiuxetan after first line treatment with chemotherapy has been shown to result in a high rate of conversion of partial to complete remissions, leading to a significant improvement in progression-free survival. Current (mostly phase II) clinical trials are investigating the role of RIT in induction or consolidation therapy after immunochemotherapy, and are incorporating RIT in high dose chemotherapy regimens followed by autologous stem cell rescue. However, phase III data are important to define the place of RIT in the treatment algorithm of patients with FL.