COMy 2026 | The role of BTK inhibitors in the current treatment landscape for WM

So, you know, when we look at BTK inhibitors as a single agent, they’re the most active, you know, class of agents. Now, of course, trying to optimize these has been very important. We don’t see with BTK inhibitor therapy complete remissions, which tells us that there are alternative pathways of survival, some of which we’ve defined, and I’m sure many others that we still have to sort of work on. But we don’t see CRs, and this tells us we can do better. We’ve tried combining BTK inhibitors with BCL-2 inhibitors. There’s currently a trial that we’re fully enrolled on combining pirtobrutinib with venetoclax. That’s actually looking promising, in the relapse/refractory setting. When we tried to do this with ibrutinib, combining venetoclax and ibrutinib, we actually saw ventricular fibrillation, and we had to abandon that trial. So all these combinations are not going to be safe. And it is really important for our viewers to understand that. There’s currently also a trial combining zanubrutinib with sonrotoclax. This is still proceeding. And so we’re going to learn about BCL-2 combinations and perhaps, you know, integrate this sort of, you know, strategy into a fixed time-limited therapy. But the ones right now, the trials that I would be looking at with great excitement are the combination of bendamustine rituximab with BTK inhibitors. There’s a trial in Canada, the BRAWM study, combining acalabrutinib with benda-R that looks wonderful. We’re seeing MRDs there. There’s a trial in China that has just also concluded combining zanubrutinib with bendamustine rituximab. A lot of MRDs there too. We’re very excited about that data. And in the U.S., we’re doing a trial with zanubrutinib and benda-R. These are slightly different trials because in the U.S., we’re trying to minimize bendamustine rituximab exposure, whereas the trials in China and in Canada are doing six cycles of bendamustine rituximab. We’ll see what the results are. We’re actually over-enrolled on that trial, so we’re really looking forward to presenting. All this data actually will be presented in Palm Springs in October at the 13th International Workshop on Waldenström. So stay tuned, more to come.

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