Splenomegaly has been considered by some to be a contraindication to monoclonal antibody immunotherapy or radioimmunotherapy because of theoretical concerns about the spleen acting as an antibody sink and limiting efficacy. IDEC-Y2B8 is a murine IgG1 kappa monoclonal antibody covalently bound to MX-DTPA (a derivative of diethylenetriamine-pentaacetic acid), which securely chelates the isotope yttrium-90. The antibody targets the CD20 antigen found on more than 90% of B-cell non-Hodgkins lymphomas (NHLs).
A phase I/II study treated 58 relapsed or refractory NHL patients (6% small lymphocyte, 65% follicular, 24% diffuse large cell [DLC] or diffuse mixed cell [DMC], 6% mantle cell) with a median age of 60 years, 29% female, and 3.8 years median time since diagnosis. Of the 58 patients, 43% had bone marrow involvement, 37% had bulky (> 7 cm single lesion) disease, 92% had prior anthracycline therapy, and 20% were resistant to all prior chemotherapy.
Adverse events were primarily hematologic, transient, and reversible. Mean serum immunoglobulin remained normal over a 1-year observation period, and only 4% of patients had a 50% decrease in immunoglobulins from baseline. Only three patients (6%) developed infections requiring hospitalization. Only 2% developed human antimurine antibody/human antichimeric antibody (HAMA/HACA) responses.
Overall response rate (ORR) was 67% (25% complete responses [CRs], 41% partial responses [PRs]), with 82% (27% CR, 56% PR) ORR in low-grade NHL patients treated at doses of 0.2, 0.3, or 0.4 mCi/kg and 89% ORR in low-grade NHL patients treated at the standard dose of 0.4 mCi/kg.
Four (50%) of eight patients who were noted to have baseline splenomegaly achieved a CR or PR, as compared with 70% (30/43) of those without splenomegaly. This difference was not statistically significant (P = .416). Six patients had complete resolution of splenomegaly, one had marked regression, and only one had no splenic response.
CONCLUSION: These phase I/II results suggest that IDEC-Y2B8 radioimmunotherapy is a safe and effective alternative for the treatment of relapsed or refractory NHL and can be used in patients with splenomegaly.