White, Christine A.

PURPOSE: Yttrium-90 ibritumomab tiuxetan (IDEC-Y2B8) is a murine immunoglobulin G1 kappa monoclonal antibody that covalently binds MX-DTPA (tiuxetan), which chelates the radioisotope yttrium-90. The antibody targets CD20, a B-lymphocyte antigen. A multicenter phase I/II trial was conducted to compare two doses of unlabeled rituximab given before radiolabeled antibody, to determine the maximum-tolerated single dose of IDEC-Y2B8 that could be administered without stem-cell support, and to evaluate safety and efficacy.PATIENTS AND METHODS: Eligible patients had relapsed or refractory (two prior regimens or anthracycline if low-grade disease) CD20+B-cell low-grade, intermediate-grade, or mantle-cell non-Hodgkin's lymphoma (NHL). There was no limit on bulky disease, and 59% had at least one mass ≥ 5 cm.RESULTS: The maximum-tolerated dose was 0.4 mCi/kg IDEC-Y2B8 (0.3 mCi/kg for patients with baseline platelet counts 100 to 149,000/μL). The overall response rate for the intent-to-treat population (n = 51) was 67% (26% complete response [CR]; 41% partial response [PR]); for low-grade disease (n = 34), 82% (26% CR; 56% PR); for intermediate-grade disease (n = 14), 43%; and for mantle-cell disease (n = 3), 0%. Responses occurred in patients with bulky disease (≥ 7 cm; 41%) and splenomegaly (50%). Kaplan-Meier estimate of time to disease progression in responders and duration of response is 12.9+ months and 11.7+ months, respectively. Adverse events were primarily hematologic and correlated with baseline extent of marrow involvement with NHL and baseline platelet count. One patient (2%) developed an anti-antibody response (human antichimeric antibody/human antimouse antibody).CONCLUSION: These phase I/II data demonstrate that IDEC-Y2B8 radioimmunotherapy is a safe and effective alternative for outpatient therapy of patients with relapsed or refractory NHL. A phase III study is ongoing.

Abstract We previously demonstrated that yttrium-90 (Y-90) ibritumomab tiuxetan (Zevalin) radioimmunotherapy (RIT) was safe and effective for relapsed or refractory CD20+, B-cell, non-Hodgkin lymphoma (NHL). We now provide long-term follow-up data in responding patients based on International Workshop Response Criteria. Complete (CR), CR unconfirmed (CRu), and partial response (PR) rates were 29%, 22%, and 22%, respectively (overall response rate 73%, 51% in CR/CRu). Mean time to progression (TTP) and duration of response (DR) in responders were 12.6 months and 11.7 months, respectively. At the maximum tolerated dose (0.4 mCi/kg [14.8 MBq/kg]), TTP and DR in complete responders (CR/CRu) were 28.3 and 27.5 months, respectively. Nine patients (24% of responding patients) had a TTP of more than 3 years. Long-term responders (> 5 years) have been identified. Ibritumomab tiuxetan produces durable responses in patients with indolent and diffuse large B-cell lymphoma. (Blood. 2004;103:4429-4431)

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 (90Y) 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 of90Y ibritumomab tiuxetan 0.4 mCi/kg (n = 73) or rituximab 375 mg/m2IV weekly for four doses (n = 70). The radioimmunotherapy group was pretreated with two rituximab doses (250 mg/m2) 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 the90Y ibritumomab tiuxetan group versus 56% for the rituximab group (P = .002). Complete response (CR) rates were 30% and 16% in the90Y 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 the90Y 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 ≥ 6 months were 64% versus 47% (P = .030). Reversible myelosuppression was the primary toxicity noted with90Y ibritumomab tiuxetan.CONCLUSION: Radioimmunotherapy with90Y ibritumomab tiuxetan is well tolerated and produces statistically and clinically significant higher ORR and CR compared with rituximab alone.