Radioimmunotherapy – still experimental? Rational, proven indications and future trends

Abstract

With the increasing incidence of Non-Hodgkin's lymphoma and still substantial disease related mortality, further improvement of therapeutic options is needed. Radioimmunotherapy (RIT) is a targeted treatment with the potential to augment the efficacy of conventional monoclonal antibodies. Out of numerous antibody – radioisotype combinations two have been approved so far: 90Y-Ibritumumab tiuxetan and 131I-Tositumomab. The tolerability of the drugs is excellent and the main side effect is protracted cytopaenia, which occurs 4–8 weeks after the treatment. Limitations of use are reduced bone marrow reserve, higher bone marrow involvement and preceding extensive radiotherapy. Results of initial trials showed promising phase I/II data for a variety of lymphoma entities. Especially in follicular lymphoma subsequent phase II/III studies now have established these drugs as single agent treatment for relapsed disease, with improved response rates when applied at an earlier disease stage. The recently released results of the so-called FIT trial helped us to additionally establish their role as consolidation treatment immediately after preceding cyclic chemotherapy. Current concepts evaluate the benefit of RIT in the context of Rituximab maintenance therapy and high dose therapy. In aggressive lymphoma, clinical efficacy of single agent treatment has been found, but nevertheless the development of the drugs in the context of consolidation treatment or as part of high dose regimens is favoured now. Upcoming results will help to identify the potential of these drugs when applied in entities like mantle cell lymphoma, diffuse large cell lymphoma or marginal zone lymphoma. Taken together, radioimmunotherapy is increasingly part of multimodal treatment algorithms, rather than a substitute for other treatment options. Moreover, given their side effect profile, radioimmunoconjugates are a highly attractive single agent option for patients with restrictions against other anti-lymphoma therapies.