Use of 90Y-ibritumomab tiuxetan in non-Hodgkin’s lymphoma

Abstract

The increase in the incidence of non-Hodgkin's lymphoma (NHL) that has occurred over recent decades is expected to continue. Therapeutic options for patients with NHL have improved over the past 20 years, but almost all patients with low-grade lymphoma and approximately 50% of patients with high-grade lymphoma eventually die of their disease, regardless of the regimen used. Thus, there is a continuing need for novel therapeutic options. One such strategy is targeted radioimmunotherapy, which is an attractive approach because lymphoma cells are inherently sensitive to radiation. 90 Y-ibritumomab tiuxetan (Zevalin; Biogen Idec Inc, San Diego, CA, and Schering AG, Berlin, Germany) was the first radioimmunotherapy agent to be approved by the US Food and Drug Administration for the treatment of patients with relapsed, low-grade B-cell NHL. 90Y-ibritumomab tiuxetan comprises the murine IgG1 anti-CD20 antibody ibritumomab, covalently linked to the beta-emitter 90 Y by a chelator tiuxetan. A prospective trial comparing 90Y-ibritumomab tiuxetan with single-agent rituximab showed an overall response rate (ORR) to 90Y-ibritumomab tiuxetan of 80% (34% complete response [CR]/unconfirmed CR [CRu]) compared with 56% (20% CR/CRu) with rituximab (P = .002). Of patients achieving a CR/CRu, 32% were still in remission at 3 to 4 years of follow-up. Similar efficacy (83% ORR, 43% CR/CRu) has been reported with 90 Y-ibritumomab tiuxetan in patients with relapsed or refractory low-grade NHL with mild thrombocytopenia (platelet counts 100,000 to 149,000/mm3 ), and in patients with rituximab-refractory NHL (ORR 74% [CR 15%] compared with an ORR 32% to last rituximab treatment). Safety data compiled from patients entered into five studies have confirmed initial observations that the toxicities encountered with 90Y-ibritumomab tiuxetan therapy are mainly hematologic and transient. As part of a consolidated clinical approach to the ongoing development of 90Y-ibritumomab tiuxetan, studies are currently being conducted in the United States and Europe to examine the role of this agent in first-line therapy of indolent NHL, in diffuse large B-cell lymphoma, and in combination with chemotherapy with peripheral blood stem cell support.