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Emerging Therapies in Non-Hodgkin Lymphoma

Research into the causes, prevention, and treatment of non-Hodgkin lymphoma is being done in many medical centers throughout the world.

Genetics
Scientists are making great progress in understanding how changes in DNA can cause normal lymphocytes to develop into lymphoma cells. This is providing insight into why these cells may grow too rapidly, live too long, and not develop into mature cells that take part in normal immune reactions. Once this is understood, drugs may be developed that block this process.

Progress in understanding DNA changes in lymphoma has already provided improved and highly sensitive tests for detecting this disease. Such tests can identify lymphoma cells based on gene changes such as translocations or rearrangements. For example, the polymerase chain reaction (PCR) test can detect one lymphoma cell among a million normal cells. Aside from being used to detect and classify lymphomas, the test is useful in helping determine if a lymphoma has been destroyed by treatment and whether a relapse is likely.

One of the more important breakthroughs in recent years has been the development of DNA microarrays. These are tests of gene patterns in a tumor’s DNA that may help spot abnormal genes in the tumor.

One of the more important breakthroughs in recent years has been the development of DNA microarrays. These are tests of gene patterns in a tumor’s DNA that may help spot abnormal genes in the tumor. This may lead to new classifications of these diseases. The tests may also be useful in identifying those patients who may need early treatment with high-dose chemotherapy and stem cell transplants. The usefulness and reliability of these tests is now being studied.

Treatment
Much of the research being done on non-Hodgkin lymphoma is focused on looking at new and better ways to treat this disease.

Chemotherapy
Many new chemotherapy drugs are being studied in clinical trials. In recent years, these studies have led to the approval of newer drugs, such as bendamustine (Treanda), for use against certain types of lymphoma. Other studies are looking at new ways to combine drugs using different doses or different sequences of drugs.

Bone Marrow and Peripheral Blood Stem Cell Transplants
Researchers continue to improve bone marrow and peripheral blood stem cell transplant methods, including new ways to collect these cells before the transplant.

Autologous (taken from the patient rather than another person) transplants have the risk of reintroducing lymphoma cells back into the patient after treatment. Researchers are testing new and improved ways to remove the last traces of lymphoma cells from these stem cell samples before they are returned to the patient. Some of the new monoclonal antibodies developed for treating lymphoma may help remove these remaining cells.

A lot of research is focusing on eliminating graft-versus-host disease in allogeneic (donor) transplants. This work revolves around altering the transplanted T-cells so that they won’t react with the recipient’s normal cells but still kill the lymphoma cells.

Researchers are also studying the effectiveness of non-myeloablative (reduced-intensity) stem cell transplants in people with lymphoma. This approach may allow more people to benefit from stem cell transplants.

Targeted Therapies
As researchers have learned more about cancer cells, they have developed newer drugs that target specific parts of these cells. These are different from standard chemotherapy drugs, which work by attacking rapidly growing cells. The newer drugs often have less serious side effects, and they may work in some cases where chemotherapy doesn’t. Targeted drugs such as bortezomib (Velcade), thalidomide (Thalomid), lenalidomide (Revlimid), and temsirolimus (Torisel) have shown some promise in treating certain lymphomas. These and similar drugs are now being studied in clinical trials.

Immunotherapy
Lymphoma cells contain certain chemicals on their surface. Monoclonal antibodies that recognize these substances can be targeted to destroy the lymphoma cells while causing little damage to normal body tissues. This treatment strategy has already proven effective. Several such drugs, including rituximab, are already available.

Rituximab is often given for a limited amount of time during treatment. Because it has few side effects, new studies are testing its long-term use to see if it helps prevent lymphomas from coming back. The use of rituximab in this type of “maintenance therapy” is still considered experimental by most doctors.

Because of the success of rituximab and similar drugs such as ibritumomab and tositumomab, new monoclonal antibodies are being developed. Some are attached to substances that can poison cancer cells, and are known as immunotoxins. They act as homing devices to deliver the toxins directly to the cancer cells. An example is an immunotoxin known as BL22, which has shown a great deal of promise in treating hairy cell leukemia (HCL) in early clinical trials.

Lymphoma Vaccines
Doctors have known for some time that people’s immune systems may help fight their cancer. In rare instances, these people’s immune systems have rejected their cancers, and they have been cured. Scientists are now trying to develop ways to encourage this immune reaction by the use of vaccines.

Unlike vaccines against infections like measles or mumps, these vaccines are designed to help treat, not prevent, lymphomas. The goal is to create an immune reaction against lymphoma cells in patients who have very early disease or in patients whose disease is in remission. One possible advantage of these types of treatments is that they seem to have very limited side effects. So far, there have been a few successes with this approach, and it is a major area of research in lymphoma treatment. At this time lymphoma vaccines are only available in clinical trials.

BiovaxID™ is a vaccine based on the unique genetic makeup of a patient’s B-cell non-Hodgkin lymphoma. The vaccine uses a unique protein (part of an antibody called an idiotype) taken from each patient’s own lymphoma cells, which are obtained during a biopsy. This is combined with substances that boost the body’s immune response when the combination is injected into the patient. A late-stage clinical trial found that in people with follicular lymphomas that went away after chemotherapy, the vaccine lengthened the time before the lymphoma came back by more than a year. The vaccine is not yet available outside of clinical trials.

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