Current concepts of radioimmonotherapy for lymphoma.

Radioimmunotherapy (RIT) is a modern treatment for non-Hodgkin's lymphoma (NHL). It targets radiation selectively to tumors with minimal irradiation of normal cells, by using monoclonal antibodies directed to tumor associated epitopes. In the beginning, RIT is indicated for the treatment of patients with relapsed or refractory low-grade, follicular, or transformed B-cell NHL, including patients with rituximab-refractory follicular NHL. There are two radiolabeled agents that are distributed commercially in the United States for RIT: Bexxar ® consisting of 131 I-labeled tositumomab and cold (unlabeled) tositumomab and Zevalin ® consisting of 90 Y-labeled Ibritumomab and cold rituximab, while Zevalin ® is the only option available in Europe. In Australia, due to the lack of Zevalin® and Bexxar®, a new hybrid regimen consisting of rituximab (as the cold antibody) and rituximab labeled with 131 I was developed.  Recently, 90 Y-Epratuzumab, a new radiotherapeutic agent based on utility of anti-CD 22 antibody, has been introduced for the treatment of indolent NHLs. All patients should meet the following criteria: evidence of CDs expression (CD20 or CD22; usually available from biopsy material at diagnosis), confirmation of less than 25% marrow involvement, platelet counts >100,000 (preferably 150,000) and granulocyte count > 3500. Patient’s dosage is based on platelet count and body weight; for Zevalin ® regimen the dose is 15 MBq/kg if platelets exceed 150K, or 11 MBq/kg for platelet counts between 100K-150K. The dose of Bexxar ® is based on whole body radiation absorbed dose determined by measuring whole body counts on 3 occasions after administration of 185 MBq of the 131 I-tositumomab. In both regimens, cold antibody (Zevalin®; rituximab- a chimeric monoclonal antibody, and Bexxar®; tositumomab- a murine monoclonal antibody) is infused prior to the radiolabeled component (Zevalin®; 90 Y-labeled anti-CD20 antibody inbitumomab, and  Bexxar®; 131 I-labeled anti-CD20 antibody tositumomab). Overall response rates of 80-100% have been reported in several studies. Recently, almost 100% of ORR has been obtained if RIT was used as the first line or consolidation therapy. In the event of relapse, patients tolerate subsequent therapy as well or better than equivalent populations who have not received RIT. Reversible transient moderate hematopoietic toxicity is the most common side effect including neutropenia and thrombocytopenia. Non-hematologic toxicities are related mostly to minor allergic reactions to the protein components of the cold antibody, mainly for patients treated with rituximab than those treated with tositumomab. RIT should not be performed in younger than 18 years old, pregnant and lactating women. Radiation exposure of family members and health care personnel is minimal, in the range of radiation safety regulations. In conclusion, radioimmunotherapy is safe, well tolerated and effective choice for NHL treatment.