When to treat people with Waldenstrom macroglobulinemia

Most experts recommend that treatment for Waldenstrom macroglobulinemia (WM) should wait until the disease is causing problems. This lets patients avoid the side effects of chemotherapy (chemo) or other drugs until they really need these medicines. In fact, studies suggest that patients who start chemo as soon as they are diagnosed do not live any longer than those who delay treatment until their WM is causing problems.

Doctors agree that hyperviscosity syndrome is a reason for immediate treatment, as it can be fatal. Other reasons for starting treatment include problems from amyloidosis and symptoms from cryoglobulinemia, as well as anemia (low red blood cells), kidney problems, heart problems, nerve damage, or any severe symptom from the WM.

Once a decision has been made to start treatment, there are several options. Treatment choices often depend on the patient's age and general health and what symptoms the patient is having. Treatment also differs if the doctor thinks that the patient may need to have a stem cell transplant in the future.

Current guidelines suggest starting treatment with one or more of the following:

• An alkylating agent (like chlorambucil or cyclophosphamide)
• A nucleoside analog (like fludarabine or cladribine),
• Rituximab (Rituxan)
• Thalidomide
• Bortezomib (Velcade)
• A corticosteroid such as dexamethasone or prednisone

These drugs are given in a variety of combinations and schedules depending on the individual situation. Some doctors like to use a combination of drugs at the beginning of treatment. In general, rituximab is not usually given by itself when the IgM level is very high because it can make the IgM level temporarily go up even higher. Also, many experts recommend avoiding the nucleoside analogs if a stem cell transplant is planned for the future. Patients should ask their doctors about schedules that are effective and convenient to them.

Many different chemotherapy combinations are used in WM, including:

• Bortezomib, dexamethasone, and rituximab (BDR)
• Chlorambucil with prednisone
• Cyclophosphamide, adriamycin, vincristine, prednisone, and rituximab (called CHOP-R)
• Cyclophosphamide, dexamethasone, and rituximab (RCD)
• Cyclophosphamide, prednisone, and rituximab (CPR)
• Bendamustine (Treanda) and rituximab
• Fludarabine and rituximab (FR)
• Thalidomide and rituximab

Other drugs and drug combinations are also used.

If a patient has hyperviscosity syndrome or if levels of the abnormal IgM protein are very high, the doctor may recommend starting plasmapheresis before chemotherapy. This procedure removes some of the abnormal IgM from the bloodstream to lower IgM levels temporarily. Plasmapheresis does not affect the lymphoma cells that make the protein, so without a treatment to kill the lymphoma cells (like chemotherapy or immunotherapy) the IgM protein will just go back up. Plasmapheresis is usually given to help the patient until the chemotherapy has a chance to work.

What if Waldenstrom macroglobulinemia doesn't respond or if it comes back after treatment?

No single treatment for WM works for all patients. If the first set of drugs doesn’t work, others drugs may be helpful. Often, a certain drug combination will work at first, but then it will seem to stop working. Most people with WM require more than one set of drugs over time. This disease is treatable, but it is not generally considered curable. High-dose chemotherapy with stem cell transplant is also an option for some patients.

If all reasonable efforts to slow the growth of the lymphoma have failed, some patients can still get relief from symptoms of WM by undergoing plasmapheresis at regular intervals to lower the levels of the abnormal IgM protein in their blood.

Sometimes WM can turn into an aggressive lymphoma. When this happens, the cancer grows much more rapidly and causes symptoms that soon become life threatening. Once aggressive lymphoma is present, treatment with a combination of several chemo drugs is usually recommended. These are the same combinations used for patients whose cancer starts out as an aggressive non-Hodgkin lymphoma (see the treatment section of our document, Non-Hodgkin Lymphoma). If combination chemo is not successful, high-dose chemo with stem cell transplantation may be an option.