GLAXOSMITHKLINE/CORIXA

New treatment for non-Hodgkin's lymphoma

Tositumomab binds to the CD20 antigen found on non-Hodgkin's lymphoma (NHL) cells, thereby initiating an immune response to the cancer. The radiolabeled monoclonal antibody, iodine I 131 tositumomab, delivers a dose of radiation directly to the cancerous cells. The treatment is indicated for patients with CD20 positive, follicular NHL, with or without transformation, whose disease is refractory to rituximab and has relapsed following chemotherapy.

Efficacy. A multicenter, single-arm study was conducted in 40 individuals to evaluate the efficacy of the tositumomab and iodine I 131 tositumomab therapeutic regimen. Overall, 35 of the 40 patients enrolled in the study met the criteria for "rituximab refractory," defined as disease with no response to rituximab or a response of less than 6 months duration. In the rituximab refractory subset, overall response was achieved in 63% (95% CI, 45­79) of patients and complete response was achieved in 29% (95% CI, 15­46) of the patients. In all patients, overall response was achieved in 68% (95% CI, 51­81) of patients and complete response was achieved in 33% (95% CI, 19­49) of the patients. The durations of response in these 2 groups were 25 and 16 months, respectively. The results of this study were supported by 4 single-arm studies (N=190) in which the overall response rates ranged from 47% to 64% and the median durations of response ranged from 12 to 18 months.

Safety. Tositumomab and iodine I 131 tositumomab are contraindicated in patients with known hypersensitivity to murine products. The most common adverse reactions associated with the therapeutic regimen are severe or life-threatening cytopenias. Other adverse reactions include the sequelae of cytopenias such as infections, hemorrhage, allergic reactions, secondary leukemia, and myelodysplasia.

Dosing. The tositumomab and iodine I 131 tositumomab therapeutic regimen is dosed in 2 steps: a dosimetric step, followed 7­14 days later by a therapeutic step. The dosimetric step consists of tositumomab 450 mg infused intravenously over 60 minutes followed by iodine I 131 tositumomab (containing 5.0 mCi I 131 and 35 mg tositumomab) infused intravenously over 20 minutes. The therapeutic step consists of tositumomab 450 mg infused intravenously of over 60 minutes followed by iodine 131 tositumomab as calculated to patient-specific activity. Throughout the therapeutic course, patients are treated with a thyro-protective regimen that includes potassium iodide.