BEXXAR Effective for Follicular Lymphoma

Tositumomab is produced in an antibiotic-free culture of mammalian cells and is composed of two mouse gamma 2a heavy chains of 451 amino acids each and two lambda light chains of 220 amino acids each. The approximate molecular weight of tositumomab is150 kD.

I-131 tositumomab is a radioiodinated derivative of tositumomab that has been covalently linked to iodine-131. Chromatographic purification steps have removed unbound radioiodine and other reactants.

The BEXXAR therapeutic regimen consists of four components administered in two steps over seven to 14 days, usually on an outpatient basis. The first set of infusions includes the nonradioactive antibody, tositumomab, used to improve the distribution in the body of the subsequent radioactive antibody and increase its uptake in the tumor, followed by a dosimetric infusion containing the antibody and a trace amount of radioactive iodine-131. The dosimetric step allows the rate of clearance of radioactivity from the body to be determined by the use of gamma camera counts obtained at three time points.

Clearance is dependent on factors such as tumor size and bone marrow involvement. From these determinations, the patient-specific amount of radioactivity necessary to deliver the targeted therapeutic total body dose of radiation can be calculated. Seven to 14 days after the dosimetric step, the patient returns for the therapeutic step, which includes two infusions, again beginning with the nonradioactive antibody, followed by the calculated patient-specific radioactivity needed to deliver the targeted total body dose of radiation.

Investigators at the University of Michigan (Ann Arbor, USA; www.umich.edu) found that 95% of 76 advanced stage lymphoma patients showed some response to BEXXAR treatment, and that 75% had a complete response, meaning no evidence of cancer remained. More than three-quarters of patients with a complete remission were disease-free after five years. The treatment was relatively mild with the most common side effect being temporary lowering of blood counts several weeks after the treatment. There was no hair loss, and nausea was rare. These findings were published in the February 3, 2005, issue of the New England Journal of Medicine.

"The results of this treatment, which essentially takes only one week to complete, rival any kind of treatment that has been used for follicular lymphoma, including chemotherapy regimens that take months to complete. It is very well tolerated by patients, and we saw complete remission in the majority of patients lasting for years,” said first author Dr. Mark Kaminski, professor of internal medicine at the University of Michigan. "Given how much better this treatment worked as first-line therapy in our study, moving this treatment up earlier in the course of a patient's illness should be strongly considered instead of using it as a last resort or not at all. These results support the notion that there is a real possibility of putting chemotherapy on the back burner for this disease.”

The University of Michigan holds patents for the BEXXAR therapeutic regimen, which is marketed by GlaxoSmithKline under a licensing agreement.