Radioimmunotherapy (RIT) in non-Hodgkin lymphoma

Abstract

Radio-labeled anti-CD20 antibodies are a relatively novel technique that uses monoclonal antibodies to target CD20-positive cells and administer complex antibody-mediated and/or complement-dependant cytotoxicity in combination with systemic radiotherapy to targeted cells and adjacent cells via the “crossfire” effect. There are currently two main agents in clinical practice—yttrium-90 (90Y) ibritumomab tiuxetan (Zevalin) and iodine-131 (131I) tositumomab (Bexxar)—with other agents in clinical development. Studies have been performed looking into the use of radioimmunotherapy (RIT) in indolent non-Hodgkin lymphoma (NHL), initially in patients with relapsed, treatment-refractory and transformed disease (overall response rates [ORR] 74–92% with complete response [CR] 15–51%), and also in patients not suitable for transplant (i.e., the elderly population [CR 23%]) and in isolation in the first-line setting (comparable response rates to RCHOP) and combination with chemotherapy in the first-line setting (ORR 90–100%). The use of RIT in diffuse large B cell aggressive (DLBC) NHL has been assessed initially in patients with relapsed disease, both rituximab naive (ORR 44%) and refractory (ORR 19%), and more recently as consolidative treatment following primary chemotherapy (early results 5-year overall survival 60% vs 37%), or in combination with primary chemotherapy. The main side effects are infusion related and hematological with a delayed nadir (4–6 weeks in DLBC NHL, 6–8 weeks in indolent disease) and correlate with bone marrow reserve.