ASH 2021 | SEQUOIA: zanubrutinib vs BR in treatment-naïve CLL/SLL
Constantine Tam, MBBS (Hons), MD, FRACP, FRCPA, The Peter MacCallum Cancer Centre, Melbourne, Australia, shares results from the Phase III SEQUOIA trial (NCT03336333) of zanubrutinib versus bendamustine plus rituximab (BR) in patients with treatment-naïve chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). Compared to BR, zanubrutinib demonstrated a significant improvement in progression-free survival. Importantly, the rates of atrial fibrillation with zanubrutinib were low. Altogether, the data from this trial support the potential use of zanubrutinib in the frontline setting for patients with treatment-naïve CLL/SLL. This interview took place at the 63rd ASH Annual Meeting and Exposition congress in Atlanta, GA.
Transcript (edited for clarity)
So this year we presented the first presentation on the zanubrutinib vs. bendamustine rituximab study. This is a study, a direct Phase III study in patients with untreated CLL who are unfit for FCR chemotherapy. And in this study, what we showed was that zanubrutinib was superior to bendamustine in terms of progression free survival, and there were important advantages in terms of tolerance as well, with reduced model suppression as an advantage for zanubrutinib...
So this year we presented the first presentation on the zanubrutinib vs. bendamustine rituximab study. This is a study, a direct Phase III study in patients with untreated CLL who are unfit for FCR chemotherapy. And in this study, what we showed was that zanubrutinib was superior to bendamustine in terms of progression free survival, and there were important advantages in terms of tolerance as well, with reduced model suppression as an advantage for zanubrutinib. The other thing of note in this study, and in the context of other studies that have gone ahead of it, it’s not surprising that a BTK inhibitor should be shown to be more effective than chemotherapy. And this is just the latest in a series of studies to show that. And an important point of note is that the rate of atrial fibrillation was actually very low in this study for zanubrutinib at 3.3%, which is not different from 2.6% of bendamustine rituximab.
So this I think is about the first study that I can remember where the BTK inhibitor arm actually did not show an excess in atrial fibrillation. And I think this really speaks to how well tolerated zanubrutinib is, in terms of its low rate of atrial fibrillation, which we already knew from randomized comparisons of zanubrutinib and ibrutinib that have been conducted in the past.
So I think what these results mean is that we now have a new option for patients for frontline CLL therapy. We are in the age of chemoimmunotherapy now. It started off as chemo-free therapy now, where patients have got chemo-free options and zanubrutinib, of all the options out there, appears to be very effective and probably has fewer side effects compared to the established ibrutinib.
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