Randomized controlled trial of yttrium-90-labeled ibritumomab tiuxetan radioimmunotherapy versus rituximab immunotherapy for patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma

Purpose: Radioimmunotherapy combines biologic and radiolytic mechanisms to target and destroy tumor cells, thus offering a needed therapeutic alternative for refractory non-Hodgkin's lymphoma (NHL) patients. This phase III randomized study compares the novel radioimmunotherapy yttrium-90 (Y-90) ibritumomab tiuxetan with a control immunotherapy, rituximab, in 143 patients with relapsed or refractory low-grade, follicular, or transformed CD20(+) transformed NHL. Patients and Methods: Patients received either a single intravenous (IV) dose of Y-90 ibritumomab tiuxetan 0.4 mCi/kg (n = 73) or rituximab 375 mg/m(2) IV weekly for four doses (n = 70). The radioimmunotherapy group was pretreated with two rituximab doses (250 mg/m(2)) to improve biodistribution and one dose of indium-111 ibritumomab tiuxetan for imaging and dosimetry. The primary end point, overall response rate (ORR), was assessed by an independent, blinded, lymphoma expert panel. Results: ORR was 80% for the Y-90 ibritumomab tiuxetan group versus 56% for the rituximab group (P = .002). Complete response (CR) rates were 30% and 16% in the Y-90 ibritumomab tiuxetan and rituximab groups, respectively (P = .04). An additional 4% achieved an unconfirmed CR in each group. Kaplan-Meier estimated median duration of response was 14.2 months in the Y-90 ibritumomab tiuxetan group versus 12.1 months in the control group (P = .6), and time to progression was 11.2 versus 10.1 months (P = .173) in all patients. Durable responses of greater than or equal to 6 months were 64% versus 47% (P = .030). Reversible myelosuppression was the primary toxicity noted with Y-90 ibritumomab tiuxetan. Conclusion: Radioimmunotherapy with Y-90 ibritum momab tiuxetan is well tolerated and produces statistically and clinically significant higher ORR and CR compared with rituximab alone. (C) 2002 by American Society of Clinical Oncology.