ERIC CLL 2026 | How is frontline fixed-duration acalabrutinib plus venetoclax shaping treatment decisions in CLL?

So, acalabrutinib and venetoclax is a very successful regimen, which results in high efficacy in patients with previously untreated CLL. It’s approved in the United States. There is very little data so far in patients with deletion 17P, but it is a very good choice for the majority of patients. It’s easy to use. It honestly has become standard in my practice, like I said, for the majority of patients. A three-month, two-to-three-month lead-in with acalabrutinib essentially fully mitigates risks of tumor lysis syndrome when you introduce venetoclax, making this regimen very safe. And a fixed-duration therapy of 15 months or so is also very attractive to many patients, both from the standpoint of minimizing side effects as well as financial toxicity. Sonrotoclax, a combination of sonrotoclax, a BCL2 inhibitor, and zanubrutinib, a BTK inhibitor, is being investigated as well. I think it will have to show at least non-inferiority to acalabrutinib plus venetoclax. However, I think it will be a fairly tall order to displace acalabrutinib plus venetoclax completely. Sonrotoclax-zanubrutinib will have to show improved PFS, will have to show improved efficacy, essentially, and at least comparable safety to acalabrutinib and venetoclax. Maybe could this happen? I guess it could. However, I think given the high tolerability of acalabrutinib and venetoclax and high efficacy over time, it is maybe a little unlikely. So we certainly do want to see a longer follow-up data with acalabrutinib and venetoclax, but so far the three-year follow-up results are very good with the majority of patients remaining in remission despite a fairly low rate of MRD in that study.

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