Treating Waldenstrom Macroglobulinemia

The drugs used to treat WM can be given in a variety of combinations and schedules depending on the situation.

Some doctors like to combine drugs (often some type of chemotherapy plus rituximab). Others prefer to start with a single drug. A person’s age, overall health, and symptoms can also affect which treatments doctors recommend.

Possible drugs used for initial treatment

Some of the following drugs and combinations might be used as the first treatment for WM. This list is in alphabetical order, not in order of importance or preference.

• Bendamustine, with or without rituximab
• Bortezomib, with or without dexamethasone and/or rituximab
• Carfilzomib, rituximab, and dexamethasone
• Cyclophosphamide, prednisone, and rituximab (CPR)
• Ibrutinib, with or without rituximab
• Ixazomib, rituximab, and dexamethasone
• Rituximab
• Rituximab, cyclophosphamide, and dexamethasone (RCD) with or without bortezomib
• Zanubrutinib

Other drugs and drug combinations can also be used.

Gene changes and WM treatment

Doctors are now using the presence or absence of certain gene changes (MYD88 and CXCR4) to decide what initial treatment may be best. Ask your cancer care team which regimen they recommend based on your situation.

What to expect during initial treatment

During treatment, you will have regular visits with your cancer care team. They will ask you about your symptoms, do physical exams, and test your blood to see how well treatment is working.

In most people with WM, the disease responds to treatment within a few months. IgM levels go down and symptoms get better.

If WM responds to initial treatment

If the WM responds, options include close monitoring for signs of disease progression or getting rituximab on a regular schedule to help keep the disease in check.

No single treatment for WM works for every person. If the first drug or set of drugs doesn’t work, other drugs may be helpful.

Most people with WM will need treatment with different drugs at some point. Often, a certain drug or combination of drugs works at first, but over time it might stop working. Or a person might stop treatment because the WM is under control, only to have it come back later.

If the WM remains under control for at least a year after the first treatment, giving the same drug(s) again may bring the cancer back under control.

If the cancer comes back sooner, or if initial treatment doesn’t work well, switching to another drug or drug combination is likely to be a better option. Many of the same drugs and combinations listed above as first-line treatments might be helpful here.

Other drugs used for treatment

The following drugs and combinations might also be used. This list is in alphabetical order, not in order of preference or importance.

• Acalabrutinib
• Bendamustine and rituximab
• Bortezomib, dexamethasone, and rituximab
• Cladribine, with or without rituximab
• Everolimus
• Fludarabine, with or without rituximab
• Fludarabine, cyclophosphamide, and rituximab
• Ibrutinib, with or without rituximab
• Ixazomib, rituximab, and dexamethasone
• Pirtobrutinib
• Rituximab
• Rituximab, cyclophosphamide and dexamethasone or prednisone
• Venetoclax
• Zanubrutinib

If chemo isn’t successful

If combination chemo is not successful, targeted therapies, high-dose chemo with a stem cell transplant, or clinical trials may be an option. Some people find relief from symptoms by getting plasmapheresis to lower the levels of the abnormal IgM protein in their blood.

When WM turns into aggressive lymphoma

Sometimes WM can turn into an aggressive lymphoma. This is called histologic transformation. When this happens, the cancer grows much more quickly and causes symptoms that can soon become life threatening.

These lymphomas are usually treated with a combination of several chemo drugs like those used for people who are first diagnosed with an aggressive non-Hodgkin lymphoma (see Treating Non-Hodgkin Lymphoma).

Hyperviscosity

Hyperviscosity is a condition in which blood is thickened and moves slowly due to the extra proteins (immunoglobulins) made by the cancer cells in WM.

It can cause symptoms such as:

• Headaches
• Stroke-like symptoms, such as weakness or numbness
• Vision changes (blurry vision or blind spots)

Doctors can test the viscosity (thickness) of your blood with a blood sample in the lab. If your viscosity is higher than normal and you are experiencing symptoms related to this, plasmapheresis is often used.

For this procedure, your blood is removed using a large IV or a catheter placed into your vein. This is called a central venous catheter (CVC). The blood passes through a machine that takes out the extra proteins, then returns to your body through the line. With the extra proteins removed, your blood can flow freely again.

If cryoglobulins or cold agglutinin disease is present, blood warmers may be used during the plasmapheresis procedure to prevent activating the immunoglobulins.

Rituximab can also be used to lower the IgM protein level and improve blood viscosity, but it should be used carefully when the protein level is very high because it can make the IgM level temporarily go up even higher.

In asymptomatic hyperviscosity, plasmapheresis may be used first to lower the IgM level and prevent symptoms before starting rituximab or a rituximab-containing treatment plan.

Bing-Neel syndrome (BNS)

BNS is a rare complication of WM in which the cancerous B cells travel to the central nervous system (CNS). Your CNS includes your brain, spinal cord, spinal fluid (CSF), and the meninges (the covering over your brain and spinal cord).

When this happens, you can develop:

• Headaches
• Seizures
• Confusion
• Cranial nerve palsies (these can prevent your eye from moving properly, cause numbness or weakness of facial muscles, or cause other changes like trouble swallowing or using your tongue)
• Weakness in your arms or legs
• Unusual sensations or numbness through your body
• Back or nerve pain

BNS can cause the covering of the brain to look thickened on MRI imaging of the head or spine, or it can cause cancer cells to collect in tumor-like formations in the brain. Doctors can confirm BNS with a biopsy of abnormal tissue or a sample of CSF that contains cancer cells.

Sometimes, cancer cells can’t be detected on biopsy samples or CSF. But if doctors think changes on an MRI and symptoms are most likely from BNS, they may go ahead and treat it.

BNS that causes symptoms can be treated with:

• Targeted therapy (ibrutinib, zanubrutinib)
• Chemotherapy (bendamustine, cytarabine, fludarabine, methotrexate)

In rare cases, radiation can be used to treat BNS that hasn’t responded to other treatments.