Prospective, Randomized, Controlled Study of Zevalin Radioimmunotherapy Compared to Rituximab Immunotherapy for B-Cell, Non-Hodgkins Lymphoma: Interim Results

Ibritumomab tiuxetan (IDEC-Y2B8 [Zevalin]) is an anti-CD20 murine immunoglobulin G1 (IgG₁) kappa monoclonal antibody conjugated to tiuxetan (MXDTPA), which can securely chelate either indium-111 (¹¹¹In) for imaging/dosimetry or yttrium-90 (⁹⁰Y) for therapy.

Rituximab (Rituxan), the chimeric human/mouse anti-CD20 monoclonal antibody derived from ibritumomab, binds complement and induces complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC). Both antibodies are capable of inducing apoptosis. ⁹⁰Y is a pure beta-emitter with significantly higher beta-energy (2.3 vs 0.6 MeV) than iodine-131(¹³¹I; historically, the first isotope used for radioimmunotherapy) and a significantly longer pathlength (c₉₀ = 5 vs 1 mm).

We performed a prospective, randomized, controlled trial comparing the ibritumomab tiuxetan regimen with a standard course of rituximab in 143 patients with relapsed or refractory low-grade, follicular, or transformed CD20+, B-cell, non-Hodgkin’s lymphoma (NHL). Patients were stratified by histologic type to International Working Formulation (IWF) category A (small lymphocytic and lymphoplasmacytic), follicular, or transformed NHL.

The ibritumomab tiuxetan regimen consisted of: 250 mg/m² of rituximab on day 0, followed by 5 mCi of ¹¹¹In-labeled ibritumomab tiuxetan (for imaging and dosimetry) and 250 mg/m² of rituximab plus 0.4 mCi/kg of ⁹⁰Y-conjugated ibritumomab tiuxetan on day 7. The rituximab-treated patients received four weekly doses of 375 mg/m².

A prospectively defined interim analysis was performed on the first 90 treated patients to assess the accuracy of response rate estimates. There was no statistical difference between the ibritumomab tiuxetan and rituximab groups with respect to the following variables: median age (60 vs 57 years); bone-marrow involvement (45% vs 39%); splenomegaly (9% vs 4%); bulky disease ³ 7 cm (19% vs 19%); prior therapy regimens (2 vs 2); elevated lactate dehydrogenase (LDH; 9% vs 11%); chemotherapy resistance (64% vs 67%); performance status; or extranodal disease. Response was classified by a LEXCOR (Lymphoma Experts Confirmation of Response) panel that was blinded to the study arms and responses assigned by the investigators.

To date, adverse events have been as previously reported with each regimen. Interim analysis revealed that the overall response rate (ORR) was 80% for the ibritumomab tiuxetan group vs 44% for the rituximab group (P < .001).

CONCLUSION: This interim analysis finds a statistically significant difference in ORR between the ⁹⁰Y-based radioimmunotherapy, ibritumomab tiuxetan, and rituximab immunotherapy for patients with relapsed or refractory low-grade, follicular, or transformed CD20+, B-cell NHL. Final conclusions await completion of this study.

Click here for Dr. Bruce Cheson’s commentary on this abstract.