High-dose
chemotherapy and autologous
stem-cell transplantation (ASCT) is the standard
therapy for patients with chemosensitive-relapsed or chemosensitive-refractory aggressive
lymphoma. The use of
rituximab, an anti-CD20
monoclonal antibody, has dramatically changed the outcome of patients with aggressive
lymphoma, increasing both response and survival rates. However, despite this progress a significant proportion of patients are still refractory or relapse after frontline
rituximab-containing
therapy. Moreover, it is increasingly more difficult to rescue these patients with current salvage
chemotherapy and ASCT approaches. Novel approaches are needed for these high-risk patients, especially in the
rituximab era.
Radioimmunotherapy (RIT) is a form of targeted
therapy using the parent
monoclonal antibody to deliver radiation emitted by a conjugated
radioisotope, to the vicinity of
antigen-positive tissues. Two radioimmunoconjugates--yttrium-90
ibritumomab tiuxetan (
Zevalin) and
iodine-131 tositumomab (
Bexxar) have been in clinical use. There are multiple studies demonstrating the safety and efficacy of both agents in both indolent and aggressive
lymphoma. Radiolabeled
antibodies are ideal candidates to combine with high-dose
chemotherapy and ASCT. RIT targets radiation to disease sites while limiting exposure of uninvolved critical organs, thus it can safely replace total-body irradiation during conditioning for ASCT. The major toxicity and limiting factor in RIT is myelotoxicity that is easily reversed by stem-cell rescue. RIT can be combined at standard doses with high-dose
chemotherapy or can be given in escalated doses either alone or with high-dose
chemotherapy before ASCT. Several phase II studies have shown the safety and potential efficacy of both agents using these approaches. A small randomized study comparing standard-dose
Zevalin with combination of
carmustine,
etoposide,
cytarabine, and
melphalan (BEAM) high-dose
chemotherapy and BEAM alone suggested a survival advantage of
Zevalin-BEAM. However, a large randomized study comparing
Bexxar-BEAM and
rituximab-BEAM did not show any advantage. More studies are needed to establish the role and the dose of RIT given for ASCT.