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ASH 2025 | Targeted therapies that appear likely to impact CLL practice in the coming years
In this video, Matthew Davids, MD, Dana-Farber Cancer Institute, Boston, MA, discusses the targeted therapies that he believes are most likely to impact the treatment of chronic lymphocytic leukemia (CLL) in the next 2-3 years. Dr Davids highlights the potential of improved BCL2 inhibitors, such as sonrotoclax, and BTK degraders. This interview took place at the 67th ASH Annual Meeting and Exposition, held in Orlando, FL.
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Transcript
So over the next two to three years, I would say there’s kind of two main areas that I’m looking at in terms of the novel mechanisms here. And one is an improved BCL2 inhibitor. The sonrotoclax drug continues to have data maturing. At this ASH meeting, we saw data with sonrotoclax plus obinutuzumab as a frontline therapy. And we’ve seen at prior meetings and also updated at this meeting, zanubrutinib with sonrotoclax, both in the relapse setting as well as an upfront treatment...
So over the next two to three years, I would say there’s kind of two main areas that I’m looking at in terms of the novel mechanisms here. And one is an improved BCL2 inhibitor. The sonrotoclax drug continues to have data maturing. At this ASH meeting, we saw data with sonrotoclax plus obinutuzumab as a frontline therapy. And we’ve seen at prior meetings and also updated at this meeting, zanubrutinib with sonrotoclax, both in the relapse setting as well as an upfront treatment. At least preclinically, sonrotoclax is about 10 times more potent than venetoclax. And sonrotoclax seems to be performing very well so far in the clinic, as well as in terms of the rates of MRD and the progression-free survival. Obviously, we’re going to need longer follow-up and larger data sets with this drug, but I do think in that two to three-year time horizon, we’ll start to see that, which could lead to use of sonrotoclax once it’s approved.
The other main area that I’m excited about is BTK degrader drugs. These include the BeOne compound, BGB and the Nurix compound Bexo. These are really both very active drugs. We’ve seen at this meeting updates that include longer-term follow-up. So previously, we knew the high response rate seen with both these drugs, but now we’ve also seen good progression-free survival. For example, with the BeOne drug, we’re seeing at 18 months, not a median reached yet. So that’s looking very promising for a group of patients who have already progressed in some cases after covalent and non-covalent BTKi and venetoclax, so-called triple refractory patients, are still having durable response to BTK degraders. So I think this raises the possibility of moving these drugs up into earlier lines of therapy. And I’m aware of already phase three trials being planned with BTK degraders, and so I think over the next few years, we’ll start to see those entering the clinic.
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