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

Genetics

Scientists are making a lot of progress in understanding how changes in the DNA inside normal lymphocytes can cause them to develop into lymphoma cells. Once this is understood, medicines may be developed that block these processes.

Progress in understanding DNA changes in lymphoma cells has already led to improved tests for detecting this disease. Some of these tests are already in use, and others are being developed. They may be used to:

• Detect lymphoma cells in a biopsy sample
• Determine what type of lymphoma a person has
• Help determine if a lymphoma is likely to grow and spread, even within a certain subtype of lymphoma
• Help figure out if a certain treatment is likely to be helpful
• Help determine if a lymphoma has been destroyed by treatment or if a relapse is likely

For example, in recent years, genetic tests have shown that there are different subtypes of diffuse large B-cell lymphoma (DLBCL), even though they look the same under the microscope. These subtypes seem to have different outlooks (prognoses) and responses to treatment. The hope is that such tests can be used to help guide treatment decisions.

Treatment

Much of the research being done on NHL is focused on looking at new and better ways to treat this disease.

Chemotherapy

Many new chemotherapy drugs are being studied in clinical trials. These studies have led to the approval of medicines such as bendamustine (Treanda) and pralatrexate (Folotyn) for use against certain types of lymphoma. Other studies are looking at new ways to combine chemo drugs, either with each other or with other types of cancer medicines.

Stem cell transplants

Researchers continue to improve stem cell transplant methods, including new ways to collect the stem cells before the transplant.

Autologous transplants (which use the patient’s own stem cells rather than cells from a donor) have the risk of reintroducing lymphoma cells back into the patient after treatment. Researchers are testing new and improved ways to separate out the last traces of lymphoma cells from the stem cells before they are returned to the patient. Some of the new monoclonal antibodies developed for treating lymphoma may help remove these remaining 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, especially those who are older or in poor health.

Targeted drug therapies

As researchers have learned more about lymphoma cells, they have developed newer medicines that target specific parts of these cells. These targeted drugs are different from standard chemotherapy drugs, which work by attacking rapidly growing cells. Targeted drugs may work in some cases where chemotherapy doesn’t, and they often have different side effects.

Some targeted drugs are already being used to treat some types of NHL, and are being studied for use against other types.

Many other targeted drugs are now being studied in clinical trials.

Immunotherapy

Doctors have known for some time that people’s immune systems may help fight their cancer. Scientists are now trying to develop ways to encourage this immune reaction. Some types of immunotherapy are already being used to treat lymphoma, as discussed in Immunotherapy for Non-Hodgkin Lymphoma.

Monoclonal antibodies: Lymphoma cells have certain proteins on their surface. Monoclonal antibodies can be made to target these proteins and destroy the lymphoma cells while causing little damage to normal body tissues. This treatment strategy has already proven effective. Several such drugs, including rituximab (Rituxan), are already used to treat lymphoma.

Some newer antibodies are attached to substances that can poison cancer cells. These are known as antibody-drug conjugates (ADCs). They act as homing devices to deliver the toxins directly to the cancer cells. For example:

• Brentuximab vedotin (Adcetris) is made up of an antibody to CD30 that is attached to a cell poison. It has been shown to help treat people with anaplastic large cell lymphoma (ALCL) and is now being studied for use against other types of lymphoma.
• Moxetumomab pasudotox targets the CD22 antigen on certain lymphoma cells, bringing along a toxin known as PE38. It’s being used in clinical trials to treat hairy cell leukemia (HCL).

Other ADCs are now being studied as well.

Immune checkpoint inhibitors: Immune system cells normally have proteins that act as checkpoints to keep them from attacking other healthy cells. Cancer cells sometimes take advantage of these checkpoint proteins to avoid being attacked by the immune system. Some newer medicines, such as pembrolizumab (Keytruda) and nivolumab (Opdivo), work by blocking these checkpoints, which can boost the immune response against cancer cells. These drugs have shown promise in treating several types of cancer and are now being studied for use against some types of lymphoma.

Chimeric antigen receptor (CAR) T-cell therapy: In this treatment, immune cells called T cells are removed from the patient’s blood and altered in the lab to have specific receptors (called chimeric antigen receptors, or CARs) on their surface. These receptors can attach to proteins on the surface of lymphoma cells. The T cells are then multiplied in the lab and given back into the patient’s blood, where they can seek out the lymphoma cells and launch a precise immune attack against them.

This technique has shown encouraging results in early clinical trials against some hard-to-treat lymphomas. Doctors are still improving how they make the T cells and are learning the best ways to use them. Several CAR T-cell therapies are now FDA approved to treat certain kinds of advanced or recurrent lymphomas, and many others are now being studied in clinical trials.

Lymphoma 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 people who have very early disease or in people whose disease is in remission. One possible advantage of these types of treatments is that they seem to have very limited side effects. At this time, lymphoma vaccines are only available in clinical trials.