Radioimmunotherapy for NHL: Experience of 90Y-Ibritumomab Tiuxetan in Clinical Practice

Abstract

Radioimmunotherapy (RIT) is a novel treatment modality that combines the benefits of radiotherapy and immunotherapy, enabling multiple sites of disseminated disease to be treated simultaneously and effectively, while minimizing toxicity to normal tissues. 90Y-ibritumomab tiuxetan consists of the anti-CD20 monoclonal antibody (MAb) ibritumomab covalently linked to tiuxetan for chelation of 90Y for therapy. Early work established that a dose of 14.8 MBq/kg (0.4 mCi/kg) is safe and effective in patients with < 25% bone marrow involvement and adequate marrow reserves, as is a dose of 11.1 MBq/kg (0.3 mCi/kg) in patients with mild thrombocytopenia (platelet counts 100 × 109 – 150 × 109/l). To date, 5 clinical trials using 90Y-ibritumomab tiuxetan have been reported, one of which assessed the efficacy in rituximab-refractory patients with follicular non-Hodgkin's lymphoma (NHL) histology. Within the 54 follicular lymphoma patients, an overall response (OR) rate of 74% and a complete response (CR) rate of 15% were achieved, despite patients having received a median of 4 prior therapies and 73% having tumors ⩾ 5 cm in diameter. In addition, a major phase III randomized trial directly compared 90Y-ibritumomab tiuxetan with the unlabeled anti-CD20 MAb rituximab. Results from the randomized trial demonstrated that OR and CR rates were significantly higher with 90Y-ibritumomab tiuxetan, compared with rituximab (OR rate 80% vs. 56%, P = 0.002; CR rate 30% vs. 16%, P = 0.004). Time to progression (TTP) was 11.2 vs. 10.1 months (P = 0.173). Treatment was generally well tolerated; the primary toxicity associated with 90Y-ibritumomab tiuxetan therapy is reversible myelosuppression, which correlates with the degree of bone marrow involvement at baseline. In an integrated analysis of safety data from 5 90Y-ibritumomab tiuxetan studies, only 7% of patients were hospitalized due to infection during the treatment period. In addition, 90Y-ibritumomab tiuxetan therapy was not shown to increase the risk of developing secondary malignancies (myelodysplastic syndrome/acute myeloid leukemia), or preclude subsequent therapy upon relapse. Current investigations are focussing on the potential role of 90Y-ibritumomab tiuxetan earlier in the treatment algorithm, including as single-agent therapy for relapsed diffuse large B-cell lymphoma patients not eligible for transplantation, and consolidation treatment for low-grade NHL patients after first-line, alkylating agent-based therapy.