Skip to main content

When to Treat People with Waldenstrom Macroglobulinemia

Waldenstrom macroglobulinemia (WM) is generally not considered to be curable, but it is treatable. Many different medicines can help keep WM under control, often for long periods of time.

Not everyone with WM needs treatment right away. In fact, some people are diagnosed with WM before they even have symptoms from it. Most experts recommend that people with WM should not usually be treated until the disease is causing problems. This lets people avoid the side effects of chemotherapy (chemo), targeted therapy, or immunotherapy drugs until they really need these medicines. In fact, studies suggest that patients who delay treatment until their WM is causing problems do not live any less time than those who start treatment as soon as they are diagnosed.

Doctors agree that hyperviscosity syndrome is a reason to treat with plasmapheresis right away, because it can be life threatening. Other reasons to start treatment include problems from amyloidosis or cryoglobulins, as well as anemia (too few red blood cells), kidney or heart problems, nerve damage, or any severe symptom from the WM.

Once a decision has been made to start treatment, there are several options, depending on the patient’s age, general health, and symptoms. Treatment is also based on whether or not the patient might have a stem cell transplant in the future.

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), while others prefer to start with a single drug. The patient’s age, overall health, and symptoms can also affect which treatments are recommended.

In general, rituximab is not usually given when the IgM level is very high because it can make the IgM level temporarily go up even higher. Plasmapheresis may be used first to lower the IgM level before starting rituximab. Another option is to give rituximab along with ibrutinib because the combination can rapidly reduce the level of IgM.  

If a stem cell transplant might be used later on, many experts recommend not giving certain chemo drugs (chlorambucil, bendamustine, cladribine, or fludarabine) because they might affect the blood stem cells in the bone marrow.

Here are some of the drugs and combinations that might be used as the first treatment for WM. (This list is in alphabetical order, not by preference of which should be used first.)

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

Other drugs and drug combinations can also be used. Talk to your doctor about which regimen might be best for you based on your situation.

During treatment, you’ll have regular visits with your doctor, who will ask you about your symptoms, do physical exams, and test your blood to see how well the treatment is working. In most people with WM, the disease will respond to treatment (IgM levels will go down and symptoms will get better) within a few months, although this may take longer in people getting only rituximab . If the WM responds, options include close monitoring for signs of disease progression or giving rituximab on a regular schedule to help keep the disease in check.

If treatment doesn’t work or if the disease comes back after treatment

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

Most people with WM will require treatment with different drugs at some point. Often, a certain drug or combination of drugs will work at first, but over time it might stop working. Or a person might stop treatment if the WM is under control, only to have it come back some time later. If the WM remained under control for at least a year after the first treatment, then giving the same drug(s) again can often help bring the cancer back under control.

If the cancer comes back sooner, or if the initial treatment was not effective, then 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 that might also be tried include alemtuzumab (Campath), ofatumumab (Arzerra), or everolimus (Afinitor). High-dose chemotherapy with stem cell transplant might also be an option for some patients.

If chemotherapy or other drugs are no longer slowing the growth of the WM, some patients can still get relief from symptoms by getting 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 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 patients who are first diagnosed with an aggressive non-Hodgkin lymphoma (see Treating Non-Hodgkin Lymphoma). If combination chemo is not successful, high-dose chemo with a stem cell transplant may be an option.

The American Cancer Society medical and editorial content team

Our team is made up of doctors and oncology certified nurses with deep knowledge of cancer care as well as journalists, editors, and translators with extensive experience in medical writing.

Buske C, Leblond V, Dimopoulos M, et al. Waldenstrom’s macroglobulinaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013;24 Suppl 6:vi155–159.

Dimopoulos MA et al. Phase 3 Trial of Ibrutinib plus Rituximab in Waldenström’s Macroglobulinemia. N Engl J Med. 2018; 378:2399-2410. 

Gertz MA. Waldenström macroglobulinemia: 2017 update on diagnosis, risk stratification, and management. Am J Hematol. 2017;92:209-217.

Mazzucchelli M., Frustaci A.M., Deodato M., Cairoli R., Tedeschi A. Waldenstrom’s macroglobulinemia: an update. Mediterr J Hematol Infect Dis 2018, 10(1): e2018004, DOI:

National Comprehensive Cancer Network (NCCN). Clinical Practice Guidelines in Oncology: Waldenstrom’s macroglobulinemia/Lymphoplasmacytic lymphoma. V.1.2022. Accessed at on September 2, 2021. 

Rajkumar SV, Dispenzieri A. Chapter 104: Multiple myeloma and related disorders. In: Niederhuber JE, Armitage JO, Dorshow JH, Kastan MB, Tepper JE, eds. Abeloff’s Clinical Oncology. 5th ed. Philadelphia, Pa. Elsevier: 2014.

Last Revised: September 2, 2021

American Cancer Society Emails

Sign up to stay up-to-date with news, valuable information, and ways to get involved with the American Cancer Society.