Iodine-131 tositumomab (Bexxar®): radioimmunoconjugate therapy for indolent and transformed B-cell non-Hodgkin’s lymphoma

Abstract

Tositumomab is an immunoglobulin G murine monoclonal antibody that binds to the CD20 antigen on the surface of normal and malignant human B-cells. Tositumomab is linked covalently with iodine-131 to produce the radioimmunoconjugate iodine-131 tositumomab (Bexxar®). The iodine-131 tositumomab regimen was approved by the US Food and Drug Administration in June 2003 for the treatment of patients with CD20-positive, follicular non-Hodgkin's lymphoma, both with and without transformation, whose disease is refractory to rituximab (Rituxan®) and has relapsed following chemotherapy. The dose-limiting toxicity of iodine-131 tositumomab is bone marrow suppression and resulting cytopenias. Unlike chemotherapy, the majority of nonhematologic adverse events associated with iodine-131 tositumomab are mild to moderate in nature and usually self limited. Iodine-131 tositumomab represents one of the most active single agents for the treatment of recurrent indolent and transformed B-cell non-Hodgkin's lymphoma, as demonstrated by several clinical trials summarized in this review. At the present time, the use of radioimmunoconjugate therapy is largely limited to patients with disease refractory to rituximab therapy and transformed disease not amenable to high-dose therapy and autologous stem cell support. Longer follow-up of ongoing clinical trials should provide reassurance as to safety and insights as to the additive stem cell toxicity from iodine-131 tositumomab administration. Studies are also addressing the role of iodine-131 tositumomab as a component of initial therapy for indolent non-Hodgkin's lymphoma and in additional histologies of non-Hodgkin's lymphoma.