Waldenstrom's macroglobulinemia (WM) — also known as lymphoplasmacytic lymphoma — is a rare blood cancer that forms in cells of the immune system. It is a form of non-Hodgkin lymphoma (NHL), one of the two main categories of lymphoma. Several types of treatment options are available for people living with WM, including chemotherapy, immunotherapy, radiation therapy, targeted drugs, and stem cell transplants.

WM forms in a type of white blood cells called B lymphocytes, or B cells. B cells function as part of the immune system: They help the body recognize and fight infections with proteins known as antibodies, which are made to recognize foreign entities. The cancer cells in WM make abnormally high levels of an antibody called immunoglobulin M (IgM). The antibody molecules made by the cancer cells are all identical and are therefore called a monoclonal protein, or M protein.

WM generally forms in the bone marrow, where the cancer cells multiply and overtake the normal healthy cells This can cause a decrease in a person’s levels of red blood cells, white blood cells, and platelets. WM is an indolent, or slow-growing, form of NHL and may progress over many years before treatment is required.

There are several treatment options available for WM. A person’s recommended treatment regimen will depend on factors such as their health, disease stage, and response to other therapies.

Watch and Wait

WM is a slow-growing disease, so it may not be causing any problems at the time of diagnosis. In such cases, doctors will most likely opt for a “watch-and-wait” approach and will monitor the disease through regular follow-up visits. Regular monitoring allows for quick action should the cancer progress to a point where treatment is required.

Chemotherapy

Chemotherapy is one standard treatment option for WM. There are many types of chemotherapeutic drugs, which can be prescribed alone or in certain combinations.

One combination that may be used to treat WM is called CHOP. It comprises:

• Cyclophosphamide (sold as Cytoxan)
• Doxorubicin (also known as hydroxydaunorubicin and sold as Adriamycin)
• Vincristine sulfate (formerly sold as Oncovin)
• Prednisone

Treanda (bendamustine) is another chemotherapy drug that may be used to treat WM.

Chemotherapy is often administered with another type of drug called Rituxan (rituximab).

Immunotherapy

Immunotherapy utilizes the proteins from the immune system to fight cancer cells. Different forms of immunotherapy might be used to treat WM.

Monoclonal Antibodies

Antibodies are proteins that recognize specific molecules, called antigens, that are present on the surface of certain cells. Synthetic (laboratory-made) antibodies are called monoclonal antibodies. Rituxan is the most common monoclonal antibody used in the treatment of WM. It recognizes a molecule called CD20 that is present on the surface of B cells. This allows the drug to target WM cancer cells specifically. Rituximab can be used alone to treat WM or together with CHOP chemotherapy in a regimen known as R-CHOP.

Arzerra (ofatumumab) is another antibody drug that binds the CD20 antigen. It may be prescribed to people who cannot take rituximab.

Immunomodulating Drugs

Immunomodulating drugs help the body fight cancer by boosting a person’s natural immune system. Thalomid (thalidomide) and Revlimid (lenalidomide) are immunomodulating drugs that can be effective at treating WM, particularly in combination with rituximab.

Radiation Therapy

Radiation is not commonly used to treat WM. However, it may be used in some cases to shrink an enlarged organ such as the spleen or lymph nodes.

Plasmapheresis

People with WM may have hyperviscosity syndrome, a condition in which the blood is abnormally thick, or viscous. Hyperviscosity syndrome is caused by the high levels of IgM. Hyperviscosity syndrome is a serious condition that can cause neurological damage and bleeding, but it can be treated with plasmapheresis, or plasma exchange.

The procedure uses a machine to separate the blood cells from the plasma (the liquid part of the blood) containing the IgM protein. New plasma from a healthy donor is mixed with the blood cells and put back into the person receiving treatment. Plasmapheresis does not directly treat the cancer — it is an emergency treatment used to improve a person’s condition until the cancer itself can be treated.

Targeted Drug Therapy

Targeted drugs work by targeting and inhibiting a specific protein or group of proteins. One class of drugs, known as proteasome inhibitors, includes the drug Velcade (bortezomib). Proteasome inhibitors prevent the destruction of proteins that slow cell division, which helps to control the growth of the cancer.

The drug Imbruvica (ibrutinib) is also used to treat WM, either alone or in combination with rituximab. Ibrutinib is part of another class of drugs known as Bruton’s tyrosine kinase (BTK) inhibitors. These prevent the function of the BTK protein, which normally promotes the growth and survival of cells. Inhibiting this protein can slow the growth of WM cells.

Stem Cell Transplantation

For healthier people who are responsive to chemotherapy, a stem cell transplant (also known as a bone marrow transplant) may be recommended. This approach involves replacing the cells in a person’s bone marrow in order to increase the tolerance for higher doses of chemotherapy.

People with WM will more commonly have an autologous stem cell transplantation, in which healthy stem cells are taken from their own body and replaced after the chemotherapy has destroyed the cancer. In some cases, an allogeneic stem cell transplantation that requires stem cells from a healthy donor will be recommended.

Ongoing Research and New Treatments

Several existing targeted drugs are currently being explored as possible treatment options for WM. The U.S. Food and Drug Administration (FDA) has already approved Kyprolis (carfilzomib) — another proteasome inhibitor. The FDA also has approved a class of drugs known as mTOR inhibitors, including Afinitor (everolimus). These drugs block the mTOR cell protein, which normally helps cells grow and divide into new ones. The drug fludarabine, combined with cyclophosphamide, is also sometimes used to treat advanced or symptomatic Waldenstrom's macroglobulinemia.

Chimeric antigen receptor T-cell (CAR-T) therapy is a newer kind of treatment that involves removing immune cells called T cells from a person and engineering them to contain chimeric antigen receptors (CARs) on the surface of the cells. The cells are then put back into the person. There, they can bind to antigens on the cancer cells, using the person’s own immune system to attack the cancer cells. CAR-T therapy has been shown to be effective against WM that has failed to respond well to other treatments.

Clinical trials for potential new therapies are ongoing and are crucial for identifying improved ways to treat WM.

Talk With Others Who Understand

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