Splenomegaly has been considered by some to be a contraindication to monoclonal antibody immunotherapy or
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.
Click here for Dr. Bruce Chesons commentary on this abstract.
Oncology Decoded: Genitourinary Cancer Therapies – Teaser
February 7th 2025Manojkumar Bupathi, MD, MS, and Ben Garmezy, MD, discuss how to optimize treatment approaches for genitourinary cancers through evaluation of real-world data, sequencing strategies, and toxicity management while working to bridge care disparities between community and academic settings.