What’s new in non-Hodgkin lymphoma research and treatment?
Scientists are making a lot of 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 changes such as chromosome translocations or rearrangements or specific gene mutations. 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 and if a relapse is likely
Much of the research being done on non-Hodgkin lymphoma is focused on looking at new and better ways to treat this disease.
Many new chemotherapy drugs are being studied in clinical trials. In recent years, these studies have led to the approval of drugs such as bendamustine (Treanda) and pralatrexate (Folotyn) 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 transplants (which use stem cells from the patient rather than from another person) 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 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.
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.
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 different side effects, and they may work in some cases where chemotherapy doesn’t.
Targeted drugs such as bortezomib (Velcade), romidepsin (Istodax), and temsirolimus (Torisel) have shown some promise in treating certain lymphomas. These and similar drugs are now being studied in clinical trials.
Gastric MALT lymphoma, which is linked to infection by the bacteria Helicobacter pylori, can often be treated with antibiotics against that bacterium. MALT lymphoma of the tissues around the eye (called ocular adnexal marginal zone lymphoma) has been linked to infection with the bacterium, Chlamydophila psittaci. A recent study has shown that treating the infection with an antibiotic (doxycycline) can make this lymphoma get better and even go away. More studies may be needed before antibiotics become part of the standard treatment for this type of lymphoma.
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 and are discussed in the section “Immunotherapy for non-Hodgkin lymphoma.”
Rituximab is most often given for a limited amount of time during treatment. Because it has few side effects, it’s been studied to see if using it long-term will help prevent lymphomas from coming back and help patients live longer. It does seem to help some patients with follicular lymphoma live longer, but using it long term for other lymphomas is still being studied.
Because of the success of rituximab and similar drugs such as ibritumomab and tositumomab, new monoclonal antibodies are being developed. Examples include epratuzumab, which targets the CD22 antigen on certain lymphoma cells, and obinutuzumab, which targets the CD20 antigen.
Some newer antibodies 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. One example of this is brentuximab vedotin (Adcetris), which is made up of an antibody to CD30 that is attached to a cell poison. It has been shown to help treat patients with anaplastic large cell lymphoma (ALCL) that is not responding to treatment with chemo.
Another immunotoxin, known as CAT-3888 (BL22), targets the CD22 antigen on certain lymphoma cells, bringing along a toxin known as PE38. This drug showed a great deal of promise in treating hairy cell leukemia (HCL) in early clinical trials. A newer version of this drug, known as CAT-8015 (moxetumomab pasudotox), is now being studied for use against lymphomas.
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 using 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’s a major area of research in lymphoma treatment. At this time lymphoma vaccines are only available in clinical trials.
BiovaxIDTM 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 protein 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 has also shown promising early results against mantle cell lymphoma. It is not yet available outside of clinical trials.
Last Medical Review: 03/27/2013
Last Revised: 07/30/2014