Related Pages Non-Hodgkin Lymphoma Home Page 1 NCI's gateway for information about non-Hodgkin lymphoma. Drug Information Summaries 2 NCI's drug information summaries provide consumer-friendly information about certain drugs that are approved by the U.S. Food and Drug Administration (FDA) to treat cancer or conditions related to cancer.

Brand name(s): Bexxar®

• Approved for follicular non-Hodgkin lymphoma

Full prescribing information ³ 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
• 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).

Glossary Terms

A protein made by plasma cells (a type of white blood cell) in response to an antigen (a substance that causes the body to make a specific immune response). Each antibody can bind to only one specific antigen. The purpose of this binding is to help destroy the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen.

A type of research study that tests how well new medical approaches work in people. These studies test new methods of screening, prevention, diagnosis, or treatment of a disease. Also called clinical study.

The disappearance of all signs of cancer in response to treatment. This does not always mean the cancer has been cured. Also called complete remission.

In medicine, loss of blood from damaged blood vessels. A hemorrhage may be internal or external, and usually involves a lot of bleeding in a short time.

Too little thyroid hormone. Symptoms include weight gain, constipation, dry skin, and sensitivity to the cold. Also called underactive thyroid.

A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion.

Cancerous. Malignant tumors can invade and destroy nearby tissue and spread to other parts of the body.

A statistics term. The middle value in a set of measurements.

A type of protein made in the laboratory that can locate and bind to substances in the body, including tumor cells. There are many kinds of monoclonal antibodies. Each monoclonal antibody is made to find one substance. Monoclonal antibodies are being used to treat some types of cancer and are being studied in the treatment of other types. They can be used alone or to carry drugs, toxins, or radioactive materials directly to a tumor.

Abnormal bone marrow cells that may lead to myelogenous leukemia.

A condition in which there is a lower-than-normal number of neutrophils (a type of white blood cell).

A tiny piece of a cell found in the blood that breaks off from a large cell found in the bone marrow. Platelets help wounds heal and prevent bleeding by forming blood clots. Also called thrombocyte.

An abnormal collection of fluid between the thin layers of tissue (pleura) lining the lung and the wall of the chest cavity.

A molecule made up of amino acids that are needed for the body to function properly. Proteins are the basis of body structures such as skin and hair and of substances such as enzymes, cytokines, and antibodies.

A cell that carries oxygen to all parts of the body. Also called erythrocyte and RBC.

In medicine, describes a disease or condition that does not respond to treatment.

The percentage of patients whose cancer shrinks or disappears after treatment.

The presence of bacteria or their toxins in the blood or tissues.

A condition in which there is a lower-than-normal number of platelets in the blood. It may result in easy bruising and excessive bleeding from wounds or bleeding in mucous membranes and other tissues.