ASH 2025 | Final report of a Phase II study of venetoclax and ibrutinib in previously untreated WM

We also presented a poster with a study in which we combined the covalent BTK inhibitor called ibrutinib with a BCL2 inhibitor called venetoclax. In this study, we tried to induce a combination of therapies that will elicit a fast and deep effect in hopefully providing patients with a non-chemotherapy regimen that is finite. This study ran into some trouble because we had already accrued 45 patients out of the 50 that we were initially planned to accrue. And two of these patients, two patients, experienced a grade 5 arrhythmia, which means they died from this arrhythmia. And the etiology of the arrhythmia is unclear. We were not able to do autopsies on these patients to understand exactly what was the problem with the arrhythmia and what exactly happened there. So we don’t know very well the etiology of what had happened. But the best thing to do at the moment was to stop study therapy. So fortunately or unfortunately, some patients completed almost the two years of therapy. Some patients did not. And the median duration of treatment in the group was about 10 months. But everybody stopped at the same time. So, we continued the study follow-up. Even though the study therapy was stopped, we continued the follow-up. And so, what I presented at ASH this year as a poster is the final analysis of this study. So in this study, what we did see was that after therapy was stopped, counting from the moment in which therapy started, there was a median time to progression of three years. And in my mind, that means that out of those three years, 10 months were spent on therapy, and then about two years were spent off therapy, which leads me to believe that the combination can induce durable responses. And based on that, that really informs the need of additional trials. So we have another study in which we are combining our pirtobrutinib, which I believe is a safer agent with venetoclax, also for two years. And that was an oral presentation at ASH this year as well. So I think the combination of BTK inhibitors and BCL2 inhibitors, I think they do provide some synergistic approach to patients with Waldenstrom’s. And that, to me, is of important value because these treatments typically are given as monotherapy in an indefinite manner. So if we can treat patients with finite treatments that will allow them to be off therapy for quite some time and then maybe get retreated again with these agents in the future because they were not exposed to these treatments long enough to become resistant. So I think there is value to that specific approach. Obviously, more research is necessary to understand if that is something that we can do.

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