Ibritumomab tiuxetan (Zevalin) is a murine anti-CD20 monoclonal antibody covalently bound to the chelator tiuxetan, which can securely chelate yttrium-90. We performed a randomized controlled trial comparing the ibritumomab tiuxetan regimen with a standard course of rituximab(Drug information on rituximab) (Rituxan) in 143 patients with relapsed or refractory low-grade, follicular, or CD20-positive transformed B-cell non-Hodgkin’s lymphoma (NHL).
Patients were stratified by histologic type to International Working Formulation A (including small lymphocytic, lymphoplasmacytic, monocytoid B, and mucosal-associated lymphoid tissue), follicular, or transformed. The ibritumomab tiuxetan regimen consisted of day 0 rituximab at 250 mg/m2 followed by 5 mCi of indium-111-labeled ibritumomab tiuxetan (for imaging/dosimetry) and day 7 rituximab at 250 mg/m2 followed by 0.4 mCi/kg yttrium-90 ibritumomab tiuxetan. Control arm patients received four weekly doses of rituximab at 375 mg/m2. Baseline characteristics in the two arms were well balanced. There was no statistical difference between the ibritumomab tiuxetan and rituximab groups in median age (60 vs 57 years); median prior therapy regimens (2 vs 2); bone marrow involvement (42% vs 34%); splenomegaly (10% vs 4%); bulky disease 5 cm (45% vs 44%), 7 cm (21% vs 26%), 10 cm (8% vs 7%); elevated lactate dehydrogenase (19% vs 14%); resistance to last prior chemotherapy (49% vs 47%); International Prognostic Index risk groups; performance status; or extranodal disease.
Ibritumomab tiuxetan adverse events were primarily hematologic, transient, and reversible. Thirty-two percent of patients developed grade 4 neutropenia and 5% grade 4 thrombocytopenia. Only 5 patients (7%) required hospitalization for infection. Response was classified by a Lymphoma Experts Confirmation of Response (LEXCOR) panel, blinded to study arm and investigator assignment of response.
The overall response rate (ORR) based on International Workshop NHL response criteria was 80% in the ibritumomab tiuxetan arm vs 56% in the rituximab arm (P = .002) with 30% complete remission (CR) (ibritumomab tiuxetan) vs 16% CR (rituximab) (P = .04) and 4% CR unconfirmed in each arm. The ORRs based on IDEC protocol criteria were 73% vs 47% (P = .002). Kaplan-Meier estimates of response duration (approximately 50% patients censored) are not statistically different at 10.9+ and 11.5+ months. The Kaplan-Meier estimate of time to next anticancer therapy has not been reached for ibritumomab tiuxetan, and that for rituximab was 15.2 months. In those who have now progressed, time to next therapy was 11.5 vs 7.8 months for control.
CONCLUSION: This phase III trial demonstrates that ibritumomab tiuxetan radioimmunotherapy is safe and effective, and that its objective response rates are statistically superior to those of rituximab alone.