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-Hodgkins 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