VIII. Radioimmunotherapy in malignant lymphoma: an underused tool?

The radiosensitivity of malignant lymphomas as well as the local targeted delivery of high doses of radiation both make radioimmunotherapy (RIT) an attractive option to fully explore. Radioisotopes are linked to a monoclonal antibody and after intravenous infusion the complex binds to all cells expressing the respective antigen. In this way not only cells binding the radioimmunoconjugate are killed, but also surrounding cells in hundreds of cell layers (depending on the type of isotope used) through a crossfire/collateral damage effect. Obviously, RIT has more side-effects than treatment with cold antibodies like rituximab. However, no major damage to vital organs has been reported as local radiation doses stay (far) below acceptable dose limits. Tolerable, transient toxicity to the bone marrow, in terms of granulocytopenia and thrombocytopenia, is the most prominent feature and therefore so far in most studies only patients with <25% lymphoma cells in the marrow are eligible. On the other hand, RIT is the most effective (single) drug in the treatment of lymphoma, in particular follicular non-Hodgkin lymphoma (NHL), as will be reported below. The two most commonly used radioimmunoconjugates are [ 90 Y]ibritumomab tiuxetan (zevalin) and [ 131 I]tositumomab (bexxar). Both are based on murine anti-CD20 antibodies. Their properties are summarized in Table 1.