What’s New in Skin Lymphoma Research?

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

Genetics

As noted in What Causes Lymphoma of the Skin? scientists are making progress in learning how changes in the DNA inside normal lymphocytes can cause them to develop into lymphoma cells. Understanding these changes can provide insight into why these cells grow too quickly, live too long, and don’t develop into normal mature cells. It might also lead to new drugs that specifically target these processes.

Our understanding of these DNA changes has already led to the development of highly sensitive lab tests for detecting this disease. For example, polymerase chain reaction (PCR) is a very sensitive test that can help tell if a lymphoma has been destroyed by treatment or if a relapse is likely. These types of tests could help doctors pick out those patients who need more intensive treatment.

Skin-directed treatments

Several newer types of skin-directed treatments are now being studied for the treatment of early stage skin lymphomas.

Photodynamic therapy (PDT)

For this treatment, a light-activated drug called aminolevulinic acid (ALA) is applied to the skin lesions. A special type of laser light is then focused on the lesions. This light changes the drug that has collected inside the lymphoma cells, which kills them.

The advantage of PDT is that it can kill cancer cells with very little harm to normal cells. But because the chemical must be activated by light, it can only kill cancer cells near the surface of the skin. This limits its use to early-stage skin lymphomas that have not grown deeply into the skin. Even then, PDT might only be used if other types of skin-directed therapies are not effective. You can find out more about PDT in Photodynamic Therapy.

Topical imiquimod and resiquimod

These drugs affect a protein called TLR7. When applied to a skin lesion as a cream or gel, they can cause a local immune reaction, which can kill skin lymphoma cells. More research is needed to help determine their safety and effectiveness, although imiquimod is already available to treat some other skin conditions, so doctors can use it off-label to treat skin lymphomas.

Chemotherapy

Many clinical trials are studying newer chemotherapy drugs. One that has shown some promise in early clinical trials is forodesine. Research on this and other new drugs continues.

Other studies are looking at ways of combining drugs already known to be effective in new ways or using different doses or different sequences of these drugs.

Targeted drugs

Newer drugs known as targeted therapies have shown clear benefit in certain kinds of skin lymphoma. The drugs vorinostat (Zolinza) and romidepsin (Istodax) are forms of targeted therapy that can help treat some skin lymphomas. Doctors are now studying how to use these drugs most effectively.

Other targeted drugs are also being studied for skin lymphomas, including everolimus (Afinitor), lenalidomide (Revlimid), and bortezomib (Velcade).

Monoclonal antibodies

Lymphoma cells have certain proteins on their surface. Special man-made antibodies that recognize these proteins can be targeted to destroy the lymphoma cells while causing little damage to normal body tissues.

Several such drugs, including rituximab (Rituxan), brentuximab vedotin (Adcetris), and mogamulizumab (Poteligeo), are now being used to treat some skin lymphomas. These are discussed in Whole Body (Systemic) Treatments for Skin Lymphomas.

Many new monoclonal antibodies are now being developed as well.

Immune checkpoint inhibitors

A promising newer area of cancer treatment is immunotherapy, which helps a person’s own immune system attack cancer cells in the body. Immunotherapy drugs called checkpoint inhibitors are monoclonal antibodies that help boost the immune response. These drugs have been found to be helpful in treating many types of cancer, and some of them are now being studied for use against skin lymphomas. Examples include pembrolizumab (Keytruda), durvalumab (Imfinzi), and atezolizumab (Tecentriq). Some studies are testing these drugs along with other treatments such as radiation therapy, which might help them work better.

Stem cell transplant

High-dose chemotherapy followed by a stem cell transplant is sometimes used to treat lymphomas that no longer respond to other treatments. Researchers continue to improve stem cell transplant methods, including new ways to harvest these cells before transplantation.

A lot of research is focusing on reducing graft-versus-host disease in allogeneic transplants (using stem cells from a donor). This work involves altering the transplanted T-cells so that they won’t react with the patient’s normal cells but will still kill the lymphoma cells.