Do All Patients Diagnosed With Waldenström Macroglobulinemia Require Immediate Intervention?

At the 2022 Lymphoma, Leukemia & Myeloma Congress in New York, Morie Gertz, MD, Mayo Clinic, Rochester, MN, discusses options for managing patients with Waldenström macroglobulinemia, highlighting that not all patients diagnosed with the disease require immediate intervention.

Transcript:

Hello, I'm Professor Morie A. Gertz from the Mayo Clinic in Rochester, Minnesota, and I'm going to review my talk on Waldenström's macroglobulinemia that was presented in New York City for the annual Lymphoma, Leukemia & Myeloma Congress. I think the highlights of my presentation on management of Waldenström’s is to remember that all patients who are diagnosed do not require immediate intervention.

Many patients can be observed, because they have smoldering disease, taking a watch and wait attitude. There is no IgM threshold level that requires therapeutic intervention. This should be driven by the presence of symptoms, either due to infiltration of liver, spleen nodes, or bone marrow with resulting symptomatic anemia or thrombocytopenia.

When you see patients with an IgM monoclonal gammopathy, it's important to remember that Waldenström’s is not the only differential diagnosis. You also have to be alert for the possibility of AL amyloidosis with IgM monoclonal protein, IgM associated demyelination peripheral neuropathy, cold agglutinin disease, which is commonly associated with an IgM monoclonal protein. And finally, Type 2 Cryoglobulinemia, which invariably has a monoclonal IgM protein.

When we think about treatment of Waldenström’s, we have to remember this is an elderly population with multiple comorbidities. And as a consequence, treatment has to be kept in mind that these are likely to be patients who are long survivors, and as they get older, the likelihood of death from Waldenström’s is actually lower than the risk of death from other causes. So, they die with Waldenström’s, but don't die because of Waldenström's. And so, [in that case] highly aggressive intensive therapy with lots of toxicity would not be justified for this elderly population.

When we think about the available therapies for Waldenström's, rituximab-based cyclophosphamide-dexamethasone therapy, which is quite old, but is still highly effective, produces response rates in the mid 80% that can be durable for up to 4 years. Alternatively, another popular regimen used in the United States is rituximab and bendamustine, that can be given one or 2 days, every 28 days, with response rates in the 90% range.

Alternatively, BTK inhibitors such as ibrutinib are very popular with Waldenström's and produce outcomes identical to rituximab and bendamustine. The choice between the 2 is usually driven by a preference for indefinite therapy, which is BTK inhibitors, oral therapy, which would be BTK inhibitors, and time-limited therapy, which would favor bendamustine.

Among the BTK inhibitors, zanubrutinib has been shown to produce equivalent progression-free survival when compared with ibrutinib, but zanubrutinib has much lower rates of atrial fibrillation, and lower rates of diarrhea, as well. And so, it is overall better tolerated than ibrutinib.

When you see a patient with Waldenström macroglobulinemia, the big choice is time-limited IV therapy that causes myelosuppression, which would be cyclophosphamide or bendamustine, or an oral BTK inhibitor. But that needs to be continued indefinitely because patients will flare even if there's a temporary discontinuation of the medication. I want to thank you so very much for your attention.

Source:

Gertz, M. A. Next Steps in Waldenström Macroglobulinemia Management. Presented at Lymphoma, Leukemia & Myeloma Congress; October 18-22, 2022. New York, NY.