Waldenstrom Macroglobulinemia: Evolving Frontline Treatment

Given the advent of targeted therapy, Steven P. Treon, MD, PhD, reflects on how the frontline management of Waldenström macroglobulinemia is changing.
PUBLISHED February 15, 2019


Transcript: 

Steven P. Treon, MD, PhD: We have an evolution right now because of all the new BTK [Bruton tyrosine kinase] inhibitors that either have been approved, like ibrutinib, or are in the pipeline that have shown efficacy in patients with Waldenström macroglobulinemia. And BTK inhibitors represent a very important new mainstay of therapy for this disease. We know that in relapsed and refractory patients, ibrutinib is now approved by the FDA. This is a very, very effective drug in patients with Waldenström macroglobulinemia, producing very high response rates and even durable responses. And we also know that these drugs are effective in patients who are seeing treatment for the first time.

There’s also a study looking at the combination of ibrutinib plus rituximab alluding to the fact that we can start combining BTK inhibitors with monoclonal antibodies. So we have really a very exciting, new and bright future ahead of us. And what I think is important for patients to know is that this is all homegrown. Unlike in the past, when we borrowed drugs from other diseases and just saw how they worked in Waldenström macroglobulinemia patients, this all came because of genomic discovery and this was centered on MYD88, and knowing that MYD88 activated ibrutinib tyrosine kinase, BTK, allowed us to be able to develop BTK inhibitors for this disease. And so this is completely homegrown, and I think it really represents the future of new treatments for Waldenström macroglobulinemia.

A very good question is, how do we select today in the absence of head-to-head comparisons? And this is where I think having the skill of somebody who works in the field of Waldenström macroglobulinemia is very, very important. We try to personalize therapy around the patient. We try to take into account how fast we need a response. We try to take into account what the risks of therapy are. What are we exposing our patients to? Because some of these drugs can have long-term side effects. And it’s important, especially now that we have new drugs emerging like the BTK inhibitors, to keep some of these risks in mind from prior therapies that we used to use.

We consider both patient factors as well as disease factors. And in fact, for our practice, genomics are very important. We take into account the patient themselves, the age of the patient, and how well their physical status is. But the genomics play a big role. We want to know what their MYD88- as well as CXCR4-mutation status is, because that helps us understand the role of BTK inhibitors compared with other traditional therapeutics. So as part of the workup for our patients, being able to get the genomics is very important.

Transcript Edited for Clarity

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