ASH 2025 | Retrospective study on outcomes and safety of covalent BTK inhibitors for the treatment of MCL

In this sort of abstract, what we wanted to look at is just outcomes and safety and toxicity with some of the covalent BTK inhibitors. As we know globally, there are three covalent BTK inhibitors, acalabrutinib, zanubrutinib, and ibrutinib. Within the U.S., we only have two options, acalabrutinib and zanubrutinib, but ibrutinib was accessible for a long period of time. And so retrospectively, we look back just to sort of see outcomes in patient populations, time on treatment, progression-free survival, and to see if there was any sort of differences between the outcomes between these three BTK inhibitors. Because in theory, they all are covalent BTK inhibitors, so we wouldn’t really expect to see any efficacy differences. The more benefit for the second-generation BTK inhibitors, acalabrutinib and zanubrutinib has been more of a toxicity profile, as you have less atrial fibrillation, less rash, less infection risk. So from our abstract, what we can see, which again, with the caveat, is it is a retrospective study. So it is a limited snapshot, and it is subjective to the information available in the records. It does appear that the two second-generation BTK inhibitors probably have some beneficial progression-free survival and sort of time-to-next treatment benefits over ibrutinib. A lot of this, I would speculate, is just related to the toxicity profile of ibrutinib because the patients ideally are not able to stay on the drug as long as they are on the other second-generation BTK inhibitors. When you look at a comparison between acalabrutinib and zanubrutinib, there was no statistical difference between these two molecules, which would be expected in this situation, given that the molecules themselves both have very comparable safety profiles. Now, just to be clear, most of the patients had ibrutinib because it was extracted from the older data set. Next, the highest percentage of patients had acalabrutinib. And zanubrutinib, because of its recent approval, had a much smaller pie of the patients utilizing this medication. So, again, you do have some inequity as far as utilization of these medications, which could probably contribute to some of the results. But all in all, it fits with the suspicion that, again, the second generation BTK inhibitors is what we’re seeing in clinical practice, much more tolerable than ibrutinib. And again, it will likely be better for the patients because again, less dose reduction, less dose stoppages, and probably keeping the patients on these medications longer because unfortunately in mantle cell lymphoma, we still have a dearth of outcomes and sort of a dearth of options and dismal outcomes in the post-BTK setting. So that will invariably affect long-term outcomes if you cannot keep these patients on this medication.

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