iwCLL 2025 | The role of zanubrutinib in CLL treatment and its relative efficacy compared to other BTKis

So I think in the first line we now have the SEQUOIA as I mentioned in different cohorts. We have zanubrutinib as a very established treatment based on arm A and B superior to chemotherapy, so for patients without del17p it’s something we’ve been using and as a very widely used and accepted treatment option. For patients with del17p, the arm C of the study provided pretty similar efficacy and also CR-CRI rate compared to the zanubrutinib arm of the randomized portion of the study, basically meaning that factors like IGHV status and del17p status don’t seem to impact the efficacy of Zanubrutinib in the first line, at least with the current follow-up. So we have that as monotherapy. 

In combination with venetoclax, we reported and published the Sequoia D cohort, which looks at the combination with Venetoclax. And that’s another option that with the safety and efficacy that is there, could be utilized in patients in the first line. In the relapsed setting, of course, from ALPINE, we did have the data, and it’s continued to be shown to be effective. 

To answer your question about the relative efficacy compared to other BTK inhibitors in the absence of head-to-head trials, except for Ibrutinib where there is ALPINE data, we don’t have a direct comparison to other BTK inhibitors. But we have done a number of indirect comparisons as we’ve done in the past few years, showing that Zanubrutinib remains very effective and probably more effective than other drugs in those indirect comparisons, considering all the limitations. We have the switch study showing that patients coming off Ibrutinib or Acalabrutinib due to intolerance could remain and benefit from Zanubrutinib for efficacy. So I think overall Zanubrutinib is a drug that has its basically place in different settings for CLL patients. And, you know, we just need to follow these patients longer and learn about their long-term efficacy.

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