New and Emerging Targeted Agents for CLL: A Review of Available BTK Inhibitors

At the 2022 Lymphoma, Leukemia & Myeloma Congress in New York, Jan Burger, MD, MD Anderson Cancer Center, Houston, TX, discussed relevant genetic mutations in chronic lymphocytic leukemia (CLL) which may influence treatment decisions and reviewed safety and efficacy data on new and emerging targeted agents for these patients, focusing on BTK inhibitors.

Transcript:

Hello, my name is Jan Burger. I'm at MD Anderson Cancer Center in Houston, Texas. I'm here in New York City at the 2022 Lymphoma, Leukemia & Myeloma Congress. I was in a session which was dealing with new targeted agents in chronic lymphocytic leukemia (CLL). I was specifically asked to talk about the currently available Bruton tyrosine kinase (BTK) inhibitors which are approved for the treatment of CLL.

The treatment of CLL has dramatically changed over the last 10 years. In the past we were using chemoimmunotherapy, and now we have changed all this to the new targeted agents. That field started with the BTK inhibitor ibrutinib, which has been around since 2010. [Ibrutinib] has now been very widely used and has replaced chemoimmunotherapy, based on a number of phase 3 clinical trials which all demonstrated that the BTK inhibitors—and that ibrutinib—is superior to our previously used chemoimmunotherapy regimen, including [fludarabine, cyclophosphamide, rituximab] (FCR), which was very widely used 10 or 15 years back. Similar to bendamustine-rituximab or chlorambucil-based treatments, in large studies, ibrutinib has been superior. That's the reason why the field has shifted, and why the BTK inhibitors are now used very widely.

Then the other area to cover was [that] there's now an emergence of second generation BTK inhibitors. Acalabrutinib already has been approved for several years and is now going strong based on very good clinical trial data which, in my reading, showed that it's as active as ibrutinib in direct comparison, for example. But it has different side effect profiles. It looks like it's better in terms of cardiovascular toxicity—it's not that it has no cardiovascular toxicity, but it has a few percentages less frequency of atrial fibrillation and arterial hypertension. And, for that reason, it's attractive to patients who have a risk of developing these kind of side effects.

So that's a good alternative. Then there's another agent coming, which is zanubrutinib or Brukinsa, which is not yet approved but is likely to be approved in the near-term future. That has also gone through a number of clinical trials, including one trial, which is called the ALPINE study, which compared it side by side with ibrutinib. There, this new agent is also looking very strong. It shows very good efficacy, which might be equal or a bit higher than ibrutinib. It has a very favorable safety profile as well.

I was concluding there that we have additional choices now beyond just ibrutinib. We can use more and more second-generation agents and that's good for patients. We have choices. But overall, the big excitement is that we have these new agents. They are all very good choices.

Many patients are benefiting from that for many years already, and that's great. In the bigger picture, it is kind of supporting a moving away from relatively non-specific chemotherapy-based treatments to these more targeted agents. We see that every time we have clinic—we see how well patients are doing with these new agents. It's been very rewarding and it's good to catch up here at the conference with colleagues and discuss these new developments. But looking back over the last 10 years, it's been a great change for the better.

Source:

Burger, J. Current BTKi Updates: What Is New? How to Select Among Them? Presented at Lymphoma, Leukemia & Myeloma Congress; October 18-22, 2022. New York, NY