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Lymphoma - non-Hodgkin's; NHL; B-cell lymphomas
Biological response modifier therapy, also called immunotherapy, uses the body's own immune system to fight cancer using natural or laboratory-developed factors. These drugs are often combined with other treatments.
Monoclonal antibodies (MAbs) are the main drugs used in biologic therapy. MAbs are designed in the laboratory to produce the same effects as natural antibodies. They bind to specific proteins called antigens and make them vulnerable to attack by other factors in the immune system. Lymphomas carry antigens that provoke strong immune responses and so are particularly good candidates for MAb therapy.
Rituximab (Rituxan) was the first monoclonal antibody approved for cancer. This drug targets the CD-20 antigen, which is found on most B-cell lymphomas. It is the most commonly used biologic drug, particularly in combination with standard chemotherapy regimens.
First approved in 1997 for treatment of relapsed or refractory NHL, rituximab has received several expanded indications since that time. Rituximab is approved for:
Rituximab in combination with CHOP (a regimen called R-CHOP, or CHOP-R) is used for first-line treatment for aggressive lymphomas, with studies reporting 3-year event-free survival of 53% compared to 35% with CHOP alone. Rituximab is given by infusion. The treatment has mild-to-moderate short-term side effects, including nausea, fever, chills, hives, dizziness, and headache. Uncommon and more serious side effects are severe allergic reactions, very low blood pressure, blood abnormalities, wheezing, infections, and sudden heart events.
Rituximab has also been associated with cases of progressive multifocal leukoencephalopathy (PML), a rare and potentially deadly brain infection. Patients who experience any of the following symptoms should immediately contact their doctors:
Patients who have previously had hepatitis B, or who are at high-risk for this viral infection, should be tested before taking rituximab because the drug has been linked to reactivation of the hepatitis B virus. Patients who are HIV-positive may experience more adverse effects from rituximab than with CHOP.
Some newer MAbs are used to treat NHL by attaching radioactive molecules to them. When the drug is injected, the monoclonal antibody targets an antigen (protein) on the surface of the tumor. The radioisotope is then delivered directly into the tumor where it kills the cancer. Ibritumomab and tositumomab both target the CD-20 antigen. Treatment with these drugs takes about 7 - 9 days to complete, compared to several months for traditional chemotherapy treatments.
In general, these drugs cause fewer side effects than traditional chemotherapy. However, serious complications may include skin infections, severe allergic reactions, and temporary lowering of blood counts. Due to the radioisotope component, these drugs are also more difficult to administer than rituximab. They tend to be used if patients do not respond to rituximab.
Interferon alpha (Intron A) is used as an antiviral drug that also has properties that are effective against some common forms of NHL, particularly low-grade, follicular NHL in advanced stages. It is sometimes combined with chemotherapy regimens such as CHOP that contain an anthracycline drug (usually doxorubicin). The combination is toxic, however, and outcomes vary. For this reason, interferon is not used that often for NHL treatment.
Side Effects. Side effects of interferon include flu-like symptoms, severe depression, irritability, weight loss, vomiting, general weakness and loss of strength, and fever. About a third of patients have a severe drop in white blood cells. About 10% of patients cannot tolerate the drug's side effects.
Proteasome Inhibitors. Bortezomib (Velcade) is approved for treatment of mantle cell lymphoma in patients who have received at least one prior therapy.
Vaccines. Although still experimental, lymphoma vaccines are used to treat -- not prevent -- cancer. They are part of an immunotherapy approach called personalized medicine; each vaccine is individually tailored to the genetic composition of the patientâ ' s tumor. The vaccine is usually given a few months after a patient receives chemotherapy. Several different vaccines, including BiovaxID and MYVax, are in late-stage clinical trials.
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