Perspectives on Zanubrutinib Adoption for CLL Treatment: Margaret Krackeler, MD

Margaret Krackeler, MD, hematologist/oncologist at Kaiser Permanente in Northern California, discusses how the practice has evolved its chronic lymphocytic leukemia (CLL) treatment algorithm, particularly the transition from ibrutinib to zanubrutinib among patients receiving Bruton tyrosine kinase (BTK) inhibitor therapy. The conversation highlights how emerging evidence is translating into everyday oncology practice.

This transcript has been lightly edited for clarity.

Transcript

This study captures a systemwide transition from ibrutinib to zanubrutinib in a real-world community oncology setting. What outcomes most strongly validated this practice change once it was implemented at scale?

In a real-world practice change from ibrutinib to zanubrutinib at Kaiser Permanente in Northern California, I would say the most compelling outcomes that validated the switch were the improved tolerability and persistence with zanubrutinib as compared to ibrutinib. In our study, patients switching to zanubrutinib had fewer treatment-limiting adverse events, as well as cardiac adverse events, and most of them, 79% of these patients, did remain on zanubrutinib at the last follow-up, without any treatment-related deaths. I would say that these outcomes, supported by our real-world data, really suggest that the switch led to better real-world safety and effective use of zanubrutinib after this practice change at Kaiser Permanente in Northern California.

Most patients who switched from ibrutinib, including some who previously progressed, remained on zanubrutinib. What does this tell us about BTK inhibitor sequencing in everyday practice?

Most of our patients who switched from ibrutinib remained on zanubrutinib. As I stated earlier, 79% of the patients remained at the end of our follow-up, and we did see good tolerability on that medication. Looking at the patients who specifically had adverse events on ibrutinib, 17% of those patients ended up having a recurrence of those adverse events while on zanubrutinib, but there were low rates of treatment discontinuation of zanubrutinib with those adverse events.

I do think that our real-world data support the use of switching to a different BTK inhibitor like zanubrutinib if the first generation or a different BTK inhibitor is not tolerated. There was a small cohort of patients where we found that they were switched to zanubrutinib due to progression on ibrutinib, and that was done at the discretion of the treating provider. However, a lot more research is needed to see if that is a standard practice or something that should be adopted. More information is really needed to see if that is effective. Our small population of patients were still on zanabrutinib, even after progression of ibrutinib, but there's really not enough data to really comment on if that sequencing is appropriate for that indication.

Reference

Krackeler ML, Chee BH, Orchanian AK, et al. Real-world treatment patterns and outcomes of zanubrutinib in chronic lymphocytic leukemia and small lymphocytic leukemia (CLL/SLL). Cancer Med. Published online October 25, 2025. doi:10.1002/cam4.71300