Case: Relapsed/Refractory Waldenstrom Macroglobulinemia

Steven P. Treon, MD, PhD:This is a very interesting case. It’s a 42-year-old individual who presents with symptomatic hyperviscosity, and it’s important to understand that this an oncologic emergency. The patient is relatively young for presentation with Waldenström, but his case is quite extreme. He’s presenting with an extremely high IgM [immunoglobulin M] level and his symptoms are very much in line with symptomatic hyperviscosity. So from the get-go, one needs to look at this as an oncologic emergency. Also, what makes this case kind of interesting is that the patient also presents with bulky adenopathy. This is extremely important because as you’re thinking about how you’re going to manage this case, you’ve got to think about the fact that he’s now coming in with bulky adenopathy.

Undoubtedly, when this individual was seen in the emergency department (ED) people would have been very concerned while looking at his retinal eye exam as to why he was hemorrhaging and why he was complaining of nose bleeds and confusion. All of this would have prompted an expanded work-up by his ED doctors. The tipoff here is that he had a very high total protein level. That’s exactly what you expect to see in somebody who’s got symptomatic hyperviscosity.

Once those tips are in place, the work-up initiated by a hematologist would invariably have included getting a CBC [complete blood count], to determine what the blood level counts were, and a serum IgM. Because you would be thinking about Waldenström and symptomatic hyperviscosity, you’d get a serum protein like plasmapheresis to see if this is a monoclonal protein. You would also get CT [computed tomography] scans because the exam would reveal that he had big lymph nodes and you want to be able to get a better idea of how extensive the adenopathy is and how bulky it is.

But the key thing here is a bone marrow biopsy. In order to make the diagnosis of Waldenström, you want a bone marrow biopsy. You want to be able to look at the immunohistochemistry to understand that this is B-cell or is a lymphoplasmacytic cell entity. You also want to get molecular diagnostics while you’re doing his bone marrow biopsy so you understand what the underlying genotype is for this patient. Does he have aMYD88mutation? Does he have aCXCR4mutation? Those are the 2 key mutations that we see in patients with Waldenström macroglobulinemia.

Transcript edited for clarity.

A 42-Year-Old Male With Relapsed/Refractory Waldenström Macroglobulinemia

September 2016

• A 42-year old male presented with blurry vision and nosebleeds.
• Physical examination revealed retinal hemorrhages, adenopathy, and splenomegaly.
• Laboratories revealed a hematocrit of 18% (normal 34.8-43.6%)
  • Platelets of 50,000/mm³(normal 155,000-410,000/mm³)
  • Leukocyte count of 1,500/mm³(normal 3,800-9,200/mm³)
• Serum total protein was high prompting a workup that revealed an IgMλ monoclonal protein and serum IgM level of 12,400 mg/dL.
• CT scans showed bulky adenopathy (> 5 cm)
• A bone marrow biopsy revealed that 80% of the intertrabecular space was involved with lymphoplasmacytic lymphoma.
• Immunohistochemistry demonstrated CD20 expressing bone marrow disease.
• Molecular diagnostic testing for MYD88 and CXCR4 is pending

Treatment

• The patient began several emergent rounds of plasmapheresis, and his vision and energy improved.
• His retinal exam improved and repeat serum IgM level was 3,892 mg/dL.
• The molecular diagnostic studies showed MYD88 L265P and CXCR4 nonsense mutations to be present in the tumor cells.
• The patient received bendamustine alone for two cycles, then rituximab was added to bendamustine for 2 more cycles. He attained a major response.

September 2018

• Two years later, he relapsed with progressive adenopathy (< 5 cm), symptomatic anemia, and his serum IgM rose to 5,459 mg/dL.
• Patient was started on rituximab/ibrutinib combination therapy.