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COMy 2025 | Choosing between ibrutinib and zanubrutinib for treating Waldenström’s macroglobulinemia
Steven Treon, MD, PhD, FRCP, Dana-Farber Cancer Institute, Boston, MA, discusses key considerations when selecting between the two FDA-approved BTK inhibitors, ibrutinib and zanubrutinib, for the treatment of Waldenström’s macroglobulinemia (WM). Dr Treon highlights how genomic profiling can guide treatment decisions, alongside clinical factors such as the presence of cytopenia and the risk of atrial fibrillation. This interview took place at the 11th World Congress on Controversies in Multiple Myeloma (COMy) congress in Paris, France.
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Transcript
Well, we’re very blessed that we have two approved BTK inhibitors for the treatment of Waldenstrom’s. There are also other BTK inhibitors that are also advancing in Waldenstrom’s. We’re also now talking about non-covalent BTK inhibitors like pirtobrutinib, and soon we’ll be talking about degraders like BGB-16673 as well as the Nurix drugs...
Well, we’re very blessed that we have two approved BTK inhibitors for the treatment of Waldenstrom’s. There are also other BTK inhibitors that are also advancing in Waldenstrom’s. We’re also now talking about non-covalent BTK inhibitors like pirtobrutinib, and soon we’ll be talking about degraders like BGB-16673 as well as the Nurix drugs. This is a very exciting time for Waldenstrom’s. But how do we choose between the two approved drugs, BTK inhibitors, for Waldenstrom’s?
Well, we look at the genomics. What we’ve come to learn is that patients who are wild type, who don’t have the MYD88 mutation, benefit with zanubrutinib. Also, it looks like patients who have the CXCR4 mutation do much better on zanubrutinib than they do on ibrutinib. And this is based on the findings of the ASPEN study, which was just updated at the 12th International Workshop on Waldenstrom’s. TP53 mutated patients also appear to do better with zanubrutinib. So, genomics play a very important role.
We also do look at side effect profile. And, you know, if you have a patient who presents with pancytopenias, maybe they’re better off with ibrutinib because we see that it’s gentler on cytopenias. On the other hand, atrial fibrillation, big difference between ibrutinib and zanubrutinib. When you look at the data, patients do much better with zanubrutinib in terms of seeing a side effect of atrial fibrillation.
So, I think we’re in an era right now where we have choices, which is all good. Choices are good. But being able to understand the underlying issues around a patient, as well as predisposition for some of the side effects that we just talked about, helps determine what the best option is for a particular patient.
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