On June 27, 2003, the FDA approved Tositumomab and Iodine I 131 Tositumomab (Bexxar®, a trademark of Corixa Corp) for the treatment of CD20 positive, follicular non-Hodgkin’s lymphoma, with or without transformation, which is untreatable with Rituximab and has relapsed following chemotherapy.

Bexxar is a multi-step treatment involving a mouse monoclonal antibody (Tositumomab) linked to a radioactive molecule (Iodine I 131). Tositumomab targets a protein (CD20) that is found on the surface of normal and malignant lymphocytes.

Bexxar is administered in two discrete steps: the dosimetric and therapeutic steps. The therapeutic step is administered 7-14 days after the dosimetric step. Each step consists of a sequential infusion of 450 milligrams (mg) of Tositumomab over 60 minutes and followed by infused over 20 minutes. The Iodine I 131 Tositumomab dose administered in the dosimetric step contains 35 mg of Tositumomab and 5 mCi Iodine-131.

The Iodine I 131 Tositumomab dose administered in the therapeutic step contains 35 mg of Tositumomab and that dose of Iodine I 131 calculated to deliver 75 cGy total body irradiation. For patients with mild (NCI CTC grade 1) thrombocytopenia (a blood condition that may result in bruising and excessive bleeding) the therapeutic dose of Iodine I 131 Tositumomab is reduced; the dose in patients with thrombocytopenia is that dose of Iodine I 131 calculated to deliver 65 cGy total body irradiation.

The determination of the dose of radiation is calculated based upon the first step (the dosimetric dose). This is a complicated procedure, involving multiple calculations and specific measurements. The company (Corixa) has developed a training program to ensure that physicians and their staff are appropriately trained in prescribing and administering of the product. Bexxar will only be distributed to physicians who have successfully completed the training program.

The efficacy of Bexxar was evaluated in a multi-center, single-arm study in patients with low-grade or transformed low-grade or follicular large-cell lymphoma whose disease had not responded to, or had progressed after, Rituximab therapy. Determination of clinical benefit of Bexxar was based on evidence of durable responses without evidence of an effect on survival.

The overall response rate was 63 percent, with a median duration of response of 25 months. The complete response rate was 29 percent; the median duration of complete response has not been reached.

These findings were supported by demonstration of durable complete and partial objective responses in patients with low-grade or transformed low-grade or follicular large-cell lymphoma in four additional, single arm, multi-center studies. In these studies, the overall response rates ranged from 47 percent to 64 percent with median durations of responses ranging from 12 to 18 months.

The most serious adverse reactions observed in the clinical trials were severe and prolonged cytopenias (decreases in neutrophils, platelets, and red blood cells) and the consequences of cytopenias which included infections (sepsis), and hemorrhage in thrombocytopenic patients, allergic reactions (bronchospasm and angioedema), secondary leukemia, and myelodysplasia.

The most common adverse reactions occurring in the clinical trials included neutropenia, thromobocytopenia, and anemia that are both prolonged and severe. Less common but severe adverse reactions included pneumonia, pleural effusion, and dehydration. Additional adverse events included infusion reactions, delayed onset hypothyroidism, and the development of human anti-mouse antibodies (HAMA).

Full prescribing information is available, including clinical trial information, safety, dosing, drug-drug interactions, and contraindications.

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