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ESH CLL 2026 | Strategies to overcome BTK inhibitor resistance in CLL
Kerry Rogers, MD, The Ohio State University, Columbus, OH, discusses strategies to overcome resistance to BTK inhibitors in chronic lymphocytic leukemia (CLL), highlighting fixed-duration combination regimens such as BTK inhibitors with venetoclax that may reduce the development of resistance while providing durable remissions. This interview took place at the ESH CLL 2026 congress in Stockholm, Sweden.
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Transcript
Yeah, so I think one way to overcome resistance to BTK inhibitors and not just covalent ones is to use these fixed duration combinations of a BTK inhibitor with venetoclax or potentially anything else. Of course, venetoclax has been the most studied now, but some other agents, you know, with a different mechanism. Because if, you know, the covalent BTK inhibitors given as monotherapy are given for an extended period of time because they don’t clear out residual disease and responses deepen out to seven or more years...
Yeah, so I think one way to overcome resistance to BTK inhibitors and not just covalent ones is to use these fixed duration combinations of a BTK inhibitor with venetoclax or potentially anything else. Of course, venetoclax has been the most studied now, but some other agents, you know, with a different mechanism. Because if, you know, the covalent BTK inhibitors given as monotherapy are given for an extended period of time because they don’t clear out residual disease and responses deepen out to seven or more years. With these fixed duration regimens, you get a good reduction in disease and can stop them and remissions are durable. And the data we have so far is that mutations associated with resistance are not seen at disease recurrence. So I really think this is a great way to limit resistance. Of course, the BTK inhibitor monotherapy is highly convenient and appropriate for a lot of patients. So this strategy might not be for everybody. But I do think that is an outstanding approach. I think we also have to see how these can be sequenced in populations of patients. There’s a lot of things we don’t know, like use of a covalent BTK inhibitor, like acalabrutinib after ibrutinib, and hopefully that data will develop. You also, with the patient, could think about how many therapies they’d expect to have in their lifespan. I think that makes the difference as well.
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