A Case of Waldenstrom Macroglobulinemia

Jorge J. Castillo, MD:This case is a very typical presentation of patients with Waldenström macroglobulinemia. As we can see, this patient has pancytopenia, which means the white blood cell count, the hemoglobin levels, and the platelet counts are below normal levels. The next best step for a clear diagnosis in a patient like this is to perform a bone marrow aspiration and biopsy. That will leave us an idea of what’s happening in the patient’s body to cause this pancytopenia. In this case, we have the presence of a lymphoplasmacytic lymphoma in the marrow. When we look at the malignant cells, they have very typical markers for Waldenström macroglobulinemia. In general, it has markers that are atypical for other conditions. We do not see CD10, which is classic for follicular lymphoma. We don’t have CD5, which is classic for CLL [chronic lymphocytic leukemia] or mantle cell lymphoma. We know these features of nonspecific findings are in some way specific for Waldenström macroglobulinemia.

Once we make a certain diagnosis, we can actually confirm it. A confirmation in this case will be a genomic alteration in the gene calledMYD88. This is a genomic abnormality that we have discovered in over 90% of patients with Waldenström macroglobulinemia. In this case, as the patient presents with a lymphoplasmacytic lymphoma in the marrow and has an elevation on the serum IgM [immunoglobulin M], as well as the presence of theMYD88mutation, the likelihood that this patient has Waldenström macroglobulinemia is over 99%.

In terms of initial treatment for patients with Waldenström macroglobulinemia, we have multiple options, and it is important to understand that the treatment has to be personalized. The way we approach a patient with neuropathy is different than how we approach a patient with hyperviscosity, for example. How we approach a patient who is 55 years old is not going to be the same as how we approach a patient who is 85 years old. Age, performance status, patient symptoms, patient genomic profiling, and other factors really play a role in how we make decisions in terms of treatment options.

I think the option of using ibrutinib in this patient in the frontline setting is very reasonable, and there are many reasons for that. In 1 scenario, we do have data that show patients who carry theMYD88mutation, as this patient does, have a higher likelihood of responding well to ibrutinib. It’s a very simple treatment. Patients take 1 pill every day, and they have to take it indefinitely for as long as they can tolerate it. This reminds me of how we treat patients with diabetes, for example, or hypertension, for which patients take 1 medication as long as it is controlling the symptoms or problems. The patient continues taking it indefinitely.

I think the issue of plasmapheresis comes up a lot, specifically in patients such as this in whom IgM is elevated and viscosity is elevated, but where the patient is asymptomatic. My practice is if the patient is asymptomatic, I’d rather not use plasmapheresis. There are some issues with plasmapheresis. We need to put a central line in, and that can cause issues with bleeding, thrombosis, infections, and things like that. There are issues with blood pressure increase and decrease in patients who get plasmapheresis as well.

If the patient does not need it, we typically do not use it. Now, if the patient were symptomatic, that would be a different story. If the patient were to have any of the symptoms that we mentioned earlier or any changes in the retinal vessels, that would be a patient in whom I would use plasmapheresis. My practice is to actually use plasmapheresis at least 3 times in the first week, to make sure that we decrease the IgM levels to a manageable point that will give us time to actually institute treatments. Plasmapheresis is not definitive treatment for Waldenström macroglobulinemia, so it should be followed by actual therapy. I would discourage patients or practitioners from using plasmapheresis in somebody over time to delay therapy. I think it should be used to transition into therapy.

Transcript edited for clarity.

Case: A 65-Year-Old Female With Newly Diagnosed Waldenström Macroglobulinemia

September 2016

• A 65-year old female presented to her PCP with slowly progressing anemia for the last couple of years
• Several months prior to that, she began experiencing drenching night sweats, distended abdomen, and 15 lb weight loss
• SH: Married, exercises regularly, social drinker, non-smoker, no illicit drug use
• FH: Maternal aunt — breast cancer age 51
• Laboratory results:
  • Hemoglobin; 7 g/dL (11-13 g/dL), platelets; 55,000/mm³(155,000-410,000/mm³), and leukocyte count 1,700/mm³(3,800-9,200/mm³).
  • M-protein; 2991.3 mg/dL; IgM 4710 mg/dL (45—281 mg/dL)
  • Serum viscosity; 3.7 centipoise (cP) (1.6—1.9 cP)
  • Beta-2; 3 mg/L (0-2.7 mg/L)
  • IPSSWM: 2 Intermediate
• Bone marrow aspiration and biopsy; 40—50% B cells
• Flow cytometry; Lambda-restricted B cells that expressed CD19 and CD20
• B cells were negative for CD5, CD10, CD43, bcl-1, and bcl-6
• Allele-specific PCR; MYD88^L265Pmutation
• Diagnosis; Waldenström’s macroglobulinemia (WM)

Treatment

• Patient was started on ibrutinib (420 mg) daily with monthly follow-up visits
• After three months, her IgM was 1500 mg/dL and her serum viscosity was 1.5 cP
• Her CBC showed improvements: WBC, 5000/mm³, Hgb 15.5g/dL; platelets 180,000/mm³
• The patient was last seen on follow-up last month and she continues on ibrutinib 2 years after her initial presentation