Next-Generation BTK Degraders for Patients With Chronic Lymphocytic Leukemia

At the 2026 LL&M Winter Symposium in Amelia Island, Florida, Justin Taylor, MD, Sylvester Comprehensive Cancer Center, Miami, Florida, discusses the emerging role of Bruton's tyrosine kinase (BTK) degrader therapies in chronic lymphocytic leukemia (CLL). 

Dr Taylor highlights early-phase data showing promising safety and activity in heavily pretreated patients, with ongoing studies evaluating their role in earlier lines of therapy. 

Transcript:

Hi, I'm Justin Taylor, I'm an associate professor at the University of Miami Sylvester Comprehensive Cancer Center, and I'm here at the 2026 LL&M Winter Symposium. My talk was about BTK degrader therapies– where do we stand now and what's the future?

To recap my talk briefly, I talked about what BTK degraders are, how they're different than inhibitors. Unlike BTK inhibitors, the degraders get rid of the whole protein and that can also address BTK resistance mutations. Several companies have made BTK degraders, but currently we only have data from 3 trials and I went over the main 2 that had updates at ASH and talked a little bit about the safety. These are both phase 1 studies so I talked about the safety and efficacy, we have early signals of efficacy, and they both look very safe. These were ongoing trials and these were just updates at ASH. Things that we'll want to look out for is more data from these.

They've also now established a phase 2 dose, so they're moving into phase 2 studies where we'll be looking at how these BTK degraders can fit into our current CLL therapy. The current trials are in patients who have already received a covalent BTK inhibitor and many have also received a BCL2 inhibitor– that's the population we have the most data on. In the phase 2/3 studies that are planned, they'll be looking at earlier lines of therapy after a covalent BTK inhibitor, so potentially second line, and they will be comparing it to mostly pirtobrutinib or chemoimmunotherapy. We'll need to wait for those results to see if these drugs have efficacy and how they compare to our other treatments before we decide where they'll fit into the current standard of care line of therapy for CLL, and of course, if they'll get approved.

Those are the future directions that I talked about. I mentioned just a little bit of coming research on potential ways that patients may get resistance to degraders as well– something we need to keep an eye on for the future.

Source:

Taylor J. BTK degraders: Emerging clinical data and what lies ahead. Presented at LL&M Winter Symposium; January 30-February 1, 2026. Amelia Island, Florida.