ASH 2025 | Long-term follow-up of SEQUOIA: zanubrutinib vs bendamustine and rituximab in treatment-naive CLL

So the SEQUOIA study is a first-line study in CLL. So these are older patients who are not fit for FCR. And SEQUOIA really has a comparison between bendamustine rituximab versus zanubrutinib as first-line treatment for CLL. That’s arm A and arm B. There’s also a third arm in SEQUOIA called arm C, and these are patients who have 17P deletion at screening, where it’s not ethical to randomise them to bendamustine rituximab. So all those patients got zanubrutinib as a monotherapy. So let’s go back to the randomised component first. So the randomised component has been reported previously, that we’ve previously reported that zanubrutinib is superior to bendamustine rituximab in terms of progression-free survival but what we do have that now is we’ve got six-year update of that cohort and at the six-year mark the progression-free survival for patients who start at frontline zanubrutinib is 74% and when you allow for the impact of COVID is now 77% So it’s a nice number to have. So next time you see a patient and you start them on first-line zanubrutinib, you can say with great confidence that there’s a three in four chance that they’ll still be in remission six years from now, which is a really nice number to say to your patients. And once again, the sustained benefit of zanubrutinib over chemotherapy is maintained over time and there’s been no new safety signals of concern. Now going to arm C, which is the people who got zanubrutinib monotherapy for 17P disease. So 17P disease, P53 mutant CLL is traditionally a very bad thing. Now the arm C actually turned out to be the biggest collection of patients in the literature of 17p deletion patients receiving any therapy. And we had over 110 patients, all of whom got zanubrutinib. And with six years follow-up, their progression-free survival is actually 65%, which is very similar to patients getting zanubrutinib who do not have 17P in arm A. And what this says to us is that we now have great confidence in a large number of patients with prolonged follow-up that if you start zanubrutinib for treatment of 17P disease, that you’re going to do very well. You’re going to have a projected progression-free survival in excess of six years, and your outcomes are actually not very different from those of patients who do not have 17p. So once again zanubrutinib seems to have been able to neutralize the adverse event of most prognostic factors in CLL and in this case it has largely neutralized the prognostic impact of 17p deletion in CLL

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