Updates in Targeted Therapies for B-Cell Malignancies - Episode 11

Waldenstrom Macroglobulinemia: Indications for Treatment


Ian W. Flinn, MD, PhD: Let’s talk now about Waldenström macroglobulinemia. Matt, in the diagnostic work-up, are you looking for mutations like MYD88 or CXCR4? Is that an important part of the average work-up of someone with Waldenström?

Matthew S. Davids, MD, MMSc: We do send these mutational status tests quite frequently—in particular, the MYD88 status. I think that’s the easiest 1 to get, and it tends to be mutated in the vast majority of Waldenström patients. We can see these rare variants that have wild-type MYD88 but still have the clinical features of Waldenström with high IgM, paraprotein, etc. Generally, most patients have a mutation in MYD88. CXCR4 testing is less widely available right now. It can affect the responsiveness to drugs like ibrutinib, but it’s probably not as critical that everyone be sequenced for CXCR4 status right now.

Ian W. Flinn, MD, PhD: Let’s just jump right into it. First of all, what are some of the indications for treatment of Waldenström. It’s kind of like CLL [chronic lymphocytic leukemia]. You don’t necessarily treat everybody when they first present.

John Pagel, MD, PhD: I think it comes down to their risk factors, right? What are their risk factors for having a complication related to their Waldenström? Remember, this is a lymphoplasma-signaling disorder with an IgM component. Any IgM level constitutes Waldenström, but when that gets high, you can have a viscosity problem which leads to capillary stasis in end organs, and that’s particularly worrisome in the brain or kidneys. We want to eliminate that. If you‘re getting up with viscosity levels of 2½ or 3, you’re starting to think about treatment. Otherwise, you’re also looking at the IgM level as a marker in understanding the pace of disease. It’s similar to a lymphocyte count in CLL.

You look at the IgM level and pay close attention to that, but that’s not a driver to treatment in and of itself. That also comes down to all those other factors that we see in newer lymphoma patients. For example, what are their B symptoms? Do they have any uncontrolled weight loss, fevers, night sweats, or other such things? Adenopathy can still happen here. How big and bulky is their disease? How much disease do they have? Those criteria are still very much in play for a Waldenström patient.

I think the MYD88 and CXCR4 are important tests to know about and to do. The MYD88 can certainly help solidify the diagnosis by looking for that mutation that we call 265. It’s a leucine-to-proline change that 90% of patients with Waldenström will have.

Matt talked about CXCR4, as well. It happens in about 40% of Waldenström patients. When you see that, it means that those patients are more aggressive, but the survival isn’t any different if you have a CXCR4 mutation. It’s a test that we want to do. These are things that will help us understand how to approach patients, but they’re not drivers to treatment.

Transcript Edited for Clarity