ASH 2024 | Two-year follow-up after ibrutinib plus venetoclax in symptomatic treatment-naive WM

So this year we’re also presenting data, it’s a two-year follow-up from the ibrutinib venetoclax study that we published in Blood in 2022. So this was the first study that was combining a BTK inhibitor, in this case ibrutinib, and a BCL2 inhibitor, in this case venetoclax. This combination actually has shown to be very effective in CLL and in mantle cell lymphoma. And in Europe, this combination is actually approved to treat patients with this disease. In the United States, it’s not yet approved. So based on that clinical experience and some laboratory data from our center showing some synergism between these two agents to actually induce a higher degree of cell killing in Waldenström’s, we created this study. And this study was designed to look at or enroll 50 patients that were previously untreated with Waldenström’s and give these patients a two-year duration treatment. Now, we were enrolling about 45 patients. And then at that time, it was at the beginning of 2022, there were two events in which patients actually died from a ventricular arrhythmia. Now, these patients were patients who had cardiac history. They had hypertension and hyperlipidemia and obesity and diabetes and arrhythmias as well as coronary artery disease. But it’s very difficult for us to say, to estimate what was the actual cause of the death of these patients, these events. Mainly because we couldn’t really run autopsies on these patients. And because we were not expecting this type of outcome, we were not collecting samples along the way. So I don’t think we have a good understanding of what actually caused these problems. But we felt it was the right thing to do to stop the study treatments. So by the end of March of 2022, we stopped treatment on everybody. The median time on therapy was about 10 months. And some patients got as little as three months. And some patients have gotten as much as 22 months of therapy. With that in mind, meaning everybody had different durations of therapy, we are presenting the two-year outcome after stopping therapy. So what I can tell you is we have not yet gotten to a point in which you know, the median progression-free survival has been met. So we are still beyond the two-year mark. And I think that’s encouraging because that really means that the combination is durable when you actually stop therapy. If you think about ibrutinib as a single agent, when you stop therapy, half of the patients progress within four weeks. And when you stop venetoclax, half of the patients progress within six months. So when you give them together and then you stop therapy, you know, more than half of patients have not yet progressed more than two years out from the from treatment stopping so that really gives us a good idea that this is a durability that we can see there. And that what’s actually gave the the impetus to continue investigating this combination and that’s what you know we also started designing this study combining pirtobrutinib and venetoclax that and we’ll also be presenting as well.

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