Rituximab and Ibritumomab:
Therapeutic Monoclonal Antibodies That Treat Non-Hodgkin Lymphoma
- Non-Hodgkin lymphoma is a malignant growth of B or T cells of the lymph system.
- It has been estimated by the American Cancer Society that in 2007 alone approximately 63,000 new cases of non-Hodgkin lymphoma were diagnosed, resulting in approximately 19,000 deaths.
- In fact, about 5 million people worldwide have non-Hodgkin lymphoma, 5 to 10% of these people die every year, and the incidence of the disease is growing.
- It is the fifth most common cancer (although there are about 29 different lymphomas in this category), with an individual’s chance of developing the disease in their lifetime being about 1 in 50.
- There are a variety of treatments for patients with non-Hodgkin lymphoma, including radiation therapy, chemotherapy, immunotherapy, bone marrow transplantation, and “watch and wait” for slowly growing cases.
- In 1997, the FDA approved the use of rituximab (Rituxan) for the treatment of non-Hodgkin lymphoma.
- Rituximab is a genetically engineered chimeric (murine/human) monoclonal antibody directed against the CD20 antigen (a protein on the surfaces of B lymphocytes).
- Following binding of the antibody to CD20, the body’s defenses attack and kill the antibody marked
- Stem cells in bone marrow lack CD20, so they are uninhibited by this treatment.
- Healthy B cells can regenerate from those stem cells, after the completion of the course of rituximab treatment (given once a week for 4 to 8 weeks), and return to normal levels within several months.
- In 2006, the FDA approved the use of rituximab in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) and other anthracycline-based chemotherapy regimens.
- In addition, the use of rituximab in combination with the chemical compound methotrexate was
approved for the treatment of moderately to severely active rheumatoid arthritis in patients who had been refractory to other treatments.
- Notwithstanding some severe side effects in some patients, rituximab has been enormously successful.
- Hundreds of thousands of people worldwide who did not respond well to conventional chemotherapy have been successfully treated with rituximab.
- In fact, while the incidence of non-Hodgkin lymphoma continues to increase, since the introduction of rituximab, mortality from the disease in the United States has declined at a rate of approximately 2.3% a year.
- In 2002, the FDA approved the use of ibritumomab tiuxetan (Zevalin) together with rituximab.
- Ibritumomab is also a monoclonal antibody that targets B cells.
- However, ibritumomab is linked to a chemical chelator molecule (tiuxetan) that binds tightly to radioactive indium-111 or yttrium-90.
- Thus, a therapeutic regimen with ibritumomab tiuxetan targets tumor cells with a high dose of radiation.
- In late 2007, treatment with ibritumomab tiuxetan was priced at approximately $24,000 per month, with treatments typically lasting 1 or 2 months.
- Treatment with ibritumomab tiuxetan is quite toxic, and around half of the treated individuals experience side effects.
- Therefore, ibritumomab tiuxetan is approved only for patients who have failed to respond to other