Yttrium-90 ibritumomab tiuxetan in the treatment of non-Hodgkin lymphoma

Most cases of indolent non-Hodgkin lymphoma (NHL) are incurable with standard chemoimmunotherapy approaches, and patients with relapsed/refractory disease have progressively shorter remissions and short survival with subsequent chemotherapy regimens. This may potentially be overcome with diversification of treatment strategies to include other modalities including radiotherapy, small molecule signaling transduction inhibitors, or highdose chemotherapy with stem cell support. Yttrium-90 ibritumomab tiuxetan (Zevalin r) is a novel treatment entity for indolent NHL. A radiolabeled antibody conjugate, it consists of a murine anti-CD20 antibody linked to a chelator molecule, tiuxetan, which is bound to radioactive yttrium. Yttrium-90 ibritumomab tiuxetan is approved for use as consolidation after initial treatment of follicular lymphoma as well as single-agent therapy in relapsed/refractory B-cell NHL. Responses are seen even in patients refractory to conventional cytotoxic chemotherapy and rituximab in both indolent and aggressive NHL subtypes. Recent clinical studies have also shown that yttrium-90 ibritumomab tiuxetan has significant activity when combined with novel targeted small molecular inhibitors as well as in autologous and allogeneic transplantation - regimens. Here we review the biology underlying the efficacy of yttrium-90 ibritumomab tiuxetan in NHL and present an overview of the clinical experience with this agent in NHL. Finally, we discuss the current role of yttrium-90 ibritumomab tiuxetan in the armamentarium of treatments for NHL and possibilities for incorporating it into future NHL treatment algorithms.