FDA Approval for Tositumomab and Iodine I 131 Tositumomab
Brand name(s): Bexxar®
- Approved for follicular non-Hodgkin lymphoma
Full prescribing information is available, including clinical trial information, safety, dosing, drug-drug interactions and contraindications.
On June 27, 2003, the U.S. Food and Drug Administration (FDA) approved Tositumomab and Iodine I 131 Tositumomab (Bexxar, made by Corixa Corp.), a monoclonal antibody-based, radioimmunotherapeutic regimen for the treatment of CD-20 positive, follicular non-Hodgkin lymphoma, with or without transformation that is refractory to rituximab (Rituxan®) and has relapsed following chemotherapy.
The Bexxar therapeutic regimen is a multistep treatment involving a mouse monoclonal antibody (Tositumomab) linked to a radioactive molecule (Iodine-131). Tositumomab is a mouse monoclonal antibody that targets a protein (CD20) that is found on the surface of normal and malignant lymphocytes.
The Bexxar therapeutic regimen 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 mg of Tositumomab over 60 minutes and followed by an infusion over 20 minutes. The Iodine-131 Tositumomab dose administered in the dosimetric step contains 35 mg of Tositumomab and 5 mCi Iodine-131. The Iodine-131 Tositumomab dose administered in the therapeutic step contains 35 mg of Tositumomab and that dose of Iodine-131 calculated to deliver 75 cGy total body irradiation.
For patients with mild (NCI CTC grade 1) thrombocytopenia, the therapeutic dose of Iodine-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. The Bexxar therapeutic regimen will only be distributed to physicians who have successfully completed the training program.
The efficacy of the Bexxar therapeutic regimen was evaluated in a multicenter, 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 the Bexxar therapeutic regimen 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, multicenter 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 (neutrophils, platelets, & red blood cells)
- the sequelae of cytopenias which included infections (sepsis) and hemorrhage in thrombocytopenic patients
- allergic reactions (bronchospasm and angioedema)
- secondary leukemia
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).
This summary was provided by Richard Pazdur, M.D., director of the FDA's Division of Oncology Drug Products.
The FDA is the division of the U.S. Department of Health and Human Services charged with ensuring the safety and effectiveness of new drugs and other products. (See "Learn How Drugs and Devices Get Approved.") The FDA's mission is to promote and protect the public health by helping safe and effective products to reach the market in a timely way, and monitoring products for continued safety after they are in use.