iwCLL 2025 | Comparing zanubrutinib to AV in CLL: a MAIC of fit patients in SEQUOIA versus patients in AMPLIFY

So of course the SEQUOIA study, an important study in first line CLL, the arm A and B looking at zanubrutinib versus bendamustine rituximab that has been now presented and published even in the long-term follow-up form and showing the ongoing efficacy of zanubrutinib being superior to chemotherapy in patients without del17p irrespective of IGHV mutational status. So we have that. And of course, the arm D of the study that was a combination of zanubrutinib and venetoclax, which we first presented at ASCO, followed by a publication. And it’s the first time we’re looking at mature kind of data, both from efficacy and safety of combination of zanubrutinib and venetoclax, really providing high response rates. And you know the study is MRD-guided, and we would need to look at longer follow-up. But, you know, so these are just the basic or general SEQUOIA cohorts. 

Of course, cohort C or arm C was focused on del17p patients, the largest prospective cohort for del17p in frontline. 

One of the analyses that we looked at was looking at the fit population from SEQUOIA. And the background on that is that in the first line setting, we have SEQUOIA, which was a study that looked at patients who were either older than 65, or if they were younger, they had comorbidities that would make them eligible to be what we call BR or bendamustine rituximab candidates. So SEQUOIA arm A and B was not necessarily a fit population as the inclusion criteria. So in contrast, when you look at the study like AMPLIFY, which used acalabrutinib and venetoclax, you know, because the study used FCR or BR in the control arm, the general study population were more fit and younger in AMPLIFY. So we tried to look at the subpopulation of SEQUOIA study that were more similar to the AMPLIFY cohort to get an idea of, if I have a patient in front of me who’s considered to be fit, how do I compare the efficacy of zanubrutinib as monotherapy versus acalabrutinib plus venetoclax? So what we did, we kind of looked at, selected a population from SEQUOIA that were most similar to AMPLIFY inclusion criteria. And we also, on top of that, did a MAIC analysis. That’s a matching adjusted indirect comparison to basically complement this subgroup analysis. And the efficacy of zanubrutinib is shown to be superior compared to acalabrutinib and venetoclax in this indirect comparison. You know, of course, we’re comparing indefinite ongoing therapy with zanubrutinib versus acalabrutinib plus venetoclax, which is a fixed duration, so these are important considerations. But in general, when efficacy is the question, and that’s very commonly a question that comes from patients, I think this analysis is important and can inform our practice and the answers we provide to our patients.

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