Radioimmunotherapy for Indolent B-Cell Non-Hodgkin Lymphoma in Relapsed, Refractory and Transformed Disease

Abstract

Radioimmunotherapy (RIT) is a new treatment modality that combines the benefits of radiotherapy and immunotherapy. In RIT, a radionuclide is coupled to a monoclonal antibody, directed against an antigen expressed on tumor cells. Recently, RIT has been introduced targeting the CD20 surface antigen, which is expressed on nearly all B-cell non-Hodgkin lymphomas (NHL). Clinical experience with RIT in the treatment of patients with indolent NHL is increasing. To date, two commercially available agents are used: yttrium-90 ((90)Y)-ibritumomab tiuxetan and iodine-131 ((131)I)-tositumomab. In general, there is no organ-specific non-hematologic toxicity when a standard dose of RIT is used. Bone marrow suppression is the dose-limiting RIT toxicity; therefore, bone marrow infiltration by NHL should be investigated before treatment. Treatment-related myelodysplastic syndromes and acute myeloid leukemia after RIT are being investigated but long-term data are needed for final evaluation. Results are quite encouraging with respect to complete remission and overall response, even in pretreated patients with unconjugated monoclonal antibodies. RIT induces high response rates and a significant subgroup of patients has achieved long-term durable responses. RIT is feasible in heavily pretreated patients and does not compromise future treatments in the event of progressive disease. Randomized phase III studies are in progress to evaluate the timing of RIT in the overall management of indolent NHLInvestigations of new emerging therapeutic strategies for patients with indolent NHL are underway, with research into the feasibility of RIT as first-line therapy and in advanced disease, RIT dose escalation and combined modality approaches with autologous stem cell transplantation. The encouraging results of RIT in indolent NHL have initiated studies focusing on its benefit for patients with aggressive NHL.