Efficacy and safety of bexxar in the expanded access study: Interim report from two institutions
Genetic Association Studies
Translational Medical Research
Relapsed or refractory low-grade NHL and transformed low-grade NHL are incurable diseases. Bexxar(tm) (tositumomab and iodine I 131 tositumomab) is a novel radioimmunotherapy that combines the activity of an anti-CD20 monoclonal antibody with tumor-targeted radiation. The dosing regimen is based on individualized dosimetry to deliver a patient-specific total body radiation dose (cGy), which accounts for interpatient variability and optimize the safety and efficacy. An expanded access trial was opened in July. 1998 to allow patients with relapsed/refractory low-grade or transformed low-grade NHL to have access to this therapy. This report describes the results of 74 patients treated at 2 institutions. Median age was 58 yrs (range 29-87 yrs); histology at entry was small lymphocytic 4%, follicular small cell 45%, follicular mixed 34%, and transformed 18%; stage at entry was II4%, III 34%, and IV 60%. Patients with bulky disease (>5 cm) 30%; elevated LDH 18%, and bone marrow involvement 45%. The median number of prior chemotherapies, was 2 (range: 1-9), and 34% of patients had previously received rituximab. The Bexxar regimen consisted of Day 1 tositumomab 450mg followed by 35 mg of Iodine 131 tositumomab (5 mCi). Seven to 14 days later the patient received tositumomab 450 mg followed by a patient specific dose of Iodine 1131 tositumomab to deliver a 65 or 75 cG> total body dose. Seventy-six percent of patients responded to Bexxar with 32% achieving; a complete response. The duration of response was 19 months (95% CI: 6 mo to NR). No patient had a serious infusion reaction and infusion rates were adjusted in only 4% of patients. The most common adverse event was reversible hématologie toxicity. Grade IV neutropenia (ANC <500 cells/mm3) and thrombocytopenia (platelet count <10,000 cells/ mm3) were observed in 8.5 % and 3% of patients, respectively. These data demonstrate that Bexxar can be delivered safely to relapsed/refractory low-grade and transformed low-grade NHL patients, including those previously treated with rituximab. The efficacy and safety data are similar to that previously reported and confirm that Bexxar is a safe and effective novel therapeutic option in relapsed/refractory and transformed low-grade NHL patients.