What’s New in Waldenstrom Macroglobulinemia Research?

Research into the causes, prevention, and treatment of Waldenstrom macroglobulinemia (WM) 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 WM cells. For example, in most people with WM, the cancer cells have been found to have changes in the MYD88 gene. More recently, a smaller percentage of WM cells have been found to have changes in the CXCR4 gene. Changes in these genes have been linked with a greater chance of WM causing symptoms and requiring treatment, and seem to affect survival as well. Researchers are now looking to develop drugs that can target cells with these gene changes. Some of these drugs are now in early clinical trials.

Chemotherapy and targeted therapies

Many new drugs to treat WM are being studied in clinical trials, as well as ways to use drugs already known to be effective by combining them in new ways, using different doses, or different sequences of drugs, one after another.

Some of the newer types of drugs that have shown promise or are being tested in WM include:

• mTOR inhibitors, such as temsirolimus (Torisel)
• Proteasome inhibitors, such as ixazomib , carfilzomib (Kyprolis), and oprozomib
• Histone deacetylase (HDAC) inhibitors, such as panobinostat, romidepsin (Istodax), and belinostat (Beleodaq)
• Bruton tyrosine kinase (BTK) inhibitors, such as ACP-196, and AVL-292
• PI3K inhibitors, such as idelalisib (Zydelig) and buparlisib (BKM120)
• Aurora kinase inhibitors, such as alisertib
• BCL-2 inhibitor such as ABT-199
• A CXCR4 antibody such as ulocuplumab

Biological therapy

Another newer approach to WM treatment is the use of biological response modifiers that stimulate the patient’s immune system to attack and destroy the lymphoma cells.

For example, it has recently been found that the bone marrow support tissues (stromal cells) make a substance called interleukin 6 (IL-6). IL-6 is a strong growth factor for multiple myeloma cells. IL-6 also helps cause the bone destruction seen in myeloma. Some current research efforts are trying to develop ways to block these functions of IL-6.

Bone marrow and peripheral blood stem cell transplant

Researchers are continually improving bone marrow and peripheral blood stem cell transplant methods, as well as trying to determine how helpful this type of treatment can be for people with WM.

Vaccines

Doctors know it is possible for people with cancer to develop immune responses to their cancer. In rare instances, people’s immune systems have rejected their cancers, and they have been cured. Scientists are now studying ways to boost this immune reaction by using vaccines.

Unlike vaccines used to prevent infections, these vaccines create an immune reaction against the lymphoma cells in patients who have very early disease or whose disease is in remission but could come back or relapse. This is a major area of research in treating lymphomas (including WM), but it is still being tested in clinical trials. You might want to consider enrolling in one of these studies.