Future Directions in Treatment of Chronic Lymphocytic Leukemia (CLL) with BTK Inhibitors - Episode 6

BTK Inhibitors: Switching Therapies in CLL

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Key opinion leaders in hematology-oncology share recommendations on switching from first-generation BTK inhibitors to next-generation BTK inhibitors for the management of patients with CLL.

Bhavesh Shah, RPh, BCOP: That brings me to talking about how there are also data in terms of patients who are intolerant to 1 BTK [Bruton tyrosine kinase] inhibitor and switching them to another. We’ve seen that with ibrutinib to acalabrutinib, and there are some data emerging on ibrutinib to zanubrutinib. I want to get your perspective on that. And if somebody has been on a BTK for a long time and then you’re switching them over, would you be concerned about any mutations they may have from switching from 1 drug to another?

Ryan Jacobs, MD: To answer your first question, it’s been interesting how the utility of these next-generation BTK inhibitors has evolved over time. With initial approval, I was using acalabrutinib. It was the first second-generation BTK inhibitor to become available. I was using it almost exclusively as a switch from ibrutinib patients who were having adverse-effect issues to acalabrutinib. My clinical experience mirrored what Farrukh Awan was able to show in his small study, which looked at patients treated in that manner because of toxicities: 75% of patients were able to be switched to acalabrutinib and either have the toxicity not recur at all or recur at a significantly lower grade. Those patients were able to be maintained on BTK inhibition. That’s primarily how I was using next-generation BTK inhibitors initially, and it was great to have that option for patients. Over time, with more data that have come to light, I’ve been primarily starting new treatment with next-generation BTK inhibitors.

Back to the question about mutations, because the treatments zanubrutinib, acalabrutinib, and ibrutinib are all covalent binders of BTK at the C481S side, I don’t think switching 1 from the other is going to necessarily increase rates of resistant mutations. To the CLL [chronic lymphocytic leukemia] cell, it’s seeing the same inhibition. The occupancy rates might vary, but those tend to be in favor of next-generation BTK inhibitors.

Bhavesh Shah, RPh, BCOP: That’s the future of talking about the next-generation BTKs that we’ll be seeing. It’s focused on those patients in the relapse setting and having specifically…

Ryan Jacobs, MD: The C481S mutation?

Bhavesh Shah, RPh, BCOP: Yes, the C481S mutation.

Transcript Edited for Clarity