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Although some improvement in the treatment of non-Hodgkin's lymphoma (NHL) has been made in recent years, it has become increasingly clear that the currently available chemotherapeutic regimens are not curative for many patients, especially those with advanced (disseminated) disease. This has led to the search for newer treatment approaches in an effort to increase survival rates. Some of the newer treatments for non-Hodgkin's lymphomas that are currently being investigated include:

• Immunotherapy (Biological Therapy)
• Proteosome Inhibitors
• Purine Analogues

Immunotherapy

• Interferon-alpha - Interferons are a group of proteins produced by cells that have been infected by a virus that help the body mount an effective immune response in order to eliminate the infecting virus. Interferons can also reduce the growth and multiplication of cancer cells. One type of interferon that is being investigated as immunotherapy for certain types of non-Hodgkin's lymphomas is interferon-alpha. Although some studies have shown that interferon-alpha can cause some types of non-Hodgkin's lymphoma tumors to shrink, its role in the treatment of non-Hodgkin's lymphoma is still considered experimental.

• Monoclonal Antibody Therapy - Monoclonal antibodies are specialized proteins produced in the laboratory that are designed to specifically attach to and, with the help of the immune system, destroy lymphoma cells. One example of a monoclonal antibody that is being used for the treatment of non-Hodgkin's lymphoma is rituximab (Rituxan). Rituximab is a monoclonal antibody that preferentially seeks out and binds (attaches) to certain types of lymphoma cells that express (produce) a specific surface antigen called the CD 20 antigen. Rituximab has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of relapsed or refractory B-cell lymphomas that express the CD 20 surface antigen. Another monoclonal antibody called Campath is being used for patients with the more uncommon T-cell type non-Hodgkin's lymphoma. Campath is usually combined with other therapy such as CHOP or a nucleoside analogue such as pentostatin.

In June and July 2004, Biogen Idec and Genentech notified healthcare professionals of revisions to the WARNINGS section of the prescribing information for rituximab (Rituxan) due to reports of Hepatitis B virus (HBV) reactivation with fulminant hepatitis, hepatic failure, and death in some patients with hematologic malignancies. Persons at high risk of HBV infection should be screened before initiation of Rituxan. Carriers of hepatitis B should be closely monitored for clinical and laboratory signs of active HBV infection and for signs of hepatitis during and for up to several months following Rituxan therapy.

Despite this warning, several investigators believe that the benefit of rituximab is so significant that they are placing patients who are HBV antigen-positive on anti-viral therapy before starting treatment with rituximab. Certainly, your doctor should have a frank discussion with you weighing the risks and benefits of such an approach if you are found to be HBV antigen-positive and rituximab is being considered in the treatment protocol.

• Radioimmunotherapy - This is a specific type of immunotherapy with a monoclonal antibody that is "conjugated" (bound to) a radioactive compound known as an isotope. When administered to a patient with non-Hodgkin's lymphoma, the monoclonal antibody preferentially binds to lymphoma cells and the conjugated radioactive substance that is bound to the antibody destroys the lymphoma cells. Examples of conjugated monoclonal antibodies that are being investigated for the treatment of certain types of non-Hodgkin's lymphomas include: