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

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OncologyONCOLOGY Vol 14 No 3
Volume 14
Issue 3

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.

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.

Articles in this issue

Comparative Economic Analysis of the Treatment of Relapsed Low-Grade B-Cell Non-Hodgkin’s Lymphoma (NHL) in France Using CHOP, Fludarabine, or Rituximab
FHIT Gene, Smoking, and Cervical Cancer
Final Report on the Safety and Efficacy of Retreatment With Rituximab for Patients With Non-Hodgkins Lymphoma
Prospective, Randomized, Controlled Study of Zevalin Radioimmunotherapy Compared to Rituximab Immunotherapy for B-Cell, Non-Hodgkins Lymphoma: Interim Results
IOM Medical Error Estimates Questioned, But Legislation Considered
Less Toxic Therapies for Hodgkin’s Disease May Reduce Secondary Cancers
Preserving Fertility in Young Women With Ovarian Cancer Does Not Decrease Survival
Iodine-131 Tositumomab for Patients With Transformed, Low-Grade Non-Hodgkin’s Lymphoma: Overall Clinical Trial Experience
Survival Rates Significantly Worse For African-Americans With Endometrial Cancer
Rituximab Has Significant Activity in Patients With Chronic Lymphocytic Leukemia
Responders to Rituximab Show Continued Tumor Regression Over Time and a Progression-Free Survival That Correlates With Response Classification
PhRMA Criticizes FDA’s Proposed Rule on Antibiotic Approvals
Phase II Study of Rituximab in Combination With CHOP in Patients With Previously Untreated Intermediate- or High-Grade Non-Hodgkin’s Lymphoma
New Antibiotic Effective in Treating Gram-Positive Bacteremia
Reduced-Dose Zevalin Radioimmunotherapy for Relapsed or Refractory B-Cell Non-Hodgkin&#146;s Lymphoma Patients With Preexisting Thrombocytopenia: Report of Interim Results of a Phase II Trial
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