ESH CLL 2026 | Data supporting continuous BTKi therapy as SoC for patients with CLL

I’m really excited to be part of this debate regarding standard of care and was given the position of continuous BTK inhibitors being the standard for most patients with chronic lymphocytic leukemia (CLL), which I think is true. And I think there’s two main key arguments for this. One is just the effectiveness, and then the other is the convenience of this. On the effectiveness side, the median progression-free survival, or the only one I know of that’s been reported in a frontline setting for BTK inhibitors, is 8.9 years. And we’ve really not seen that effectiveness replicated with any other agents in the frontline setting. Granted, some of them don’t really have a median progression-free survival yet. But when we see that the progression-free survival is as good if not better with newer covalent BTK inhibitors like acalabrutinib and zanubrutinib, I really think just that’s a very strong argument to use these agents. Also, it mitigates the adverse biologic features of deletion 17p and TP53 mutation, as well as IGHV unmutated status in the frontline setting. So I think that’s really important too, because in these higher risk subgroups, particularly the TP53 disruptive patients with chronic lymphocytic leukemia (CLL), this really is much more effective than other strategies. I think the other major argument is just the convenience of these drugs. And this is something that’s extremely hard to capture in clinical trials. But when you look at what the treatment visits look like for a BTK inhibitor, these are pills people take at home. There’s limited laboratory monitoring. Yes, people need to come to clinic to understand side effects they’re having and make sure it’s working. But, you know, it’s very low burden compared to our fixation regimens, which currently use venetoclax, which requires a five-week startup and monitoring scheme, which is burdensome for patients with at least two days in a row for five weeks for monitoring and for actually physicians and treatment teams that have to look at the labs, make sure they have visits scheduled. And then if you do that with obinutuzumab, you’re looking at eight weeks of a lot of visits. And so just the convenience of a monotherapy to, you know, like one drug, you’ve only got side effects from one drug. So I think something that’s undercaptured in clinical trials, but is a key driver of BTK inhibitors as a standard is really the convenience factor. And with the newer drugs, acalabrutinib and zanubrutinib, the cardiovascular risks are lower. And we started to see some reported trial data with pirtobrutinib as a frontline, and that’s even safer. So I do think that this is going to be a really continue to be a highly utilized treatment strategy as a standard.

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