IDEC's Zev in patients who failed Rit. 46% overall response rate and no data on whether any are complete responders. Can someone help explaining why the abstract says that there was dosemitry used. I thought Zev didn't use dosemitry.
[396] ZEVALIN? (IDEC-Y2B8) RADIOIMMUNOTHERAPY OF RITUXIMAB REFRACTORY FOLLICULAR NON-HODGKIN'S LYMPHOMA (NHL): INTERIM RESULTS. Leo I. Gordon, Christine A. White, Thomas E. Witzig, Ian Flinn, Myron Czuczman, Gregory A. Wiseman, Stewart Spies, Teresa Olejnik, Charlie Zhang, Antonio J. Grillo-Lopez. Robert H. Lurie Cancer Center, Northwestern University, Chicago, IL; Medical & Regulatory Affairs, IDEC Pharmaceuticals Corp., San Diego, CA; Mayo Clinic, Hematology/Oncology & Nuclear Medicine, Rochester, MN; Oncology, Johns Hopkins Oncology Center, Baltimore, MD; Hematologic Oncology & Transplantation, Roswell Park Cancer Center, Buffalo, NY.
Zevalin (IDEC-Y2B8; generic name: ibritumomab tiuxetan) is an anti-CD20 murine IgG1 kappa monoclonal antibody conjugated to tiuxetan (MXDTPA) which forms a strong chelate with the pure beta emitting isotope 90Yttrium. Mechanisms of action include direct induction of apoptosis [Blood 1996;88(10 Suppl 1):637a] and radiolysis. Phase I/II ORR was 67% in low-grade, int-grade, and mantle cell Rituximab naive NHL patients, and 82% in Rituximab naive low-grade patients. Duration of response and TTP in responders for the 0.4mCi/kg Phase I/II cohort were 14.4 and 15.4 months respectively. Based on the Phase I/II experience, we are conducting a nonrandomized Phase III open-label clinical trial to evaluate efficacy and safety of Zevalin in follicular NHL patients refractory to Rituximab (i.e. did not achieve a response or had TTP of < 6 months with most recent course of Rituximab 375 mg/m2, weekly x4). Efficacy endpoints include ORR, duration of response, TTP, and comparison of ORR and duration to that achieved with prior therapy. Patients were excluded if they had more than 25% bone marrow involvement with NHL; > 5000 circulating lymphocytes; or prior radioimmunotherapy. Interim analysis was performed on the first 26 patients. Patient characteristics included: median age (56yrs.); follicular histology (92% of patients); median prior therapies (3); bone marrow involvement (27% of patients); splenomegaly (12% of patients); bulky disease > 7cm (46% of patients); prior radiotherapy (31% of patients). All patients who underwent dosimetry (N=23 in this interim analysis group) had acceptable biodistribution and estimated absorbed radiation doses to normal organs. Toxicity was primarily hematologic, transient, and reversible. Median hematologic nadirs were AGC 900/mm3, platelets 34,000/mm3, and Hb 10.6 gm/dl. Transient grade 4 thrombocytopenia and neutropenia occurred in 8% and 23% respectively. In these patients, median recovery occurred in 15 and 14 days respectively. Response classification was assigned by a Lymphoma Expert Confirmation of Response (LEXCOR) panel that was blinded to investigator designation of response. ORR was 46% in the 24 follicular patients for whom response data was available. Three patients were considered non-responders as their response had not been confirmed at 28 days at the time of the interim analysis. This interim analysis suggests that Zevalin radioimmunotherapy is safe and effective in the treatment of Rituximab refractory follicular NHL. Final conclusions await complete analysis.
Poster Session: Indolent Lymphoid Malignancies and Additional Therapeutic Approaches (9:45 AM-7:30 PM) |
