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ERIC CLL 2026 | Insights into the current CLL treatment algorithm and emerging research directions
Matthew Davids, Dana-Farber Cancer Institute, Boston, MA, discusses the current treatment algorithm for chronic lymphocytic leukemia (CLL) and highlights how new data are shaping his practice, noting that targeted therapies have replaced chemoimmunotherapy as the initial treatment in most countries. Dr Davids is excited about emerging areas of CLL research, including BTK degraders that may overcome resistance mechanisms and immune-based therapies that hold promise for future treatment advances. This interview took place at the 2026 ERIC International Meeting in Barcelona, Spain.
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Transcript
So we’re very fortunate now in CLL that we have a variety of targeted therapies that have been approved and are pretty widely accessible. So for most countries now, we do not need to start with chemoimmunotherapy. And really, we use a variety of different factors to help us guide patients as to the optimal therapy for them. And these include some of the genetic markers, such as IGHV status and TP53 mutation status, as well as different patient comorbidities such as cardiovascular disease or renal dysfunction...
So we’re very fortunate now in CLL that we have a variety of targeted therapies that have been approved and are pretty widely accessible. So for most countries now, we do not need to start with chemoimmunotherapy. And really, we use a variety of different factors to help us guide patients as to the optimal therapy for them. And these include some of the genetic markers, such as IGHV status and TP53 mutation status, as well as different patient comorbidities such as cardiovascular disease or renal dysfunction. And I think patient preference also plays a major role now in selecting therapy. So these are all factors that we discuss. We have a variety of new regimens that have been approved recently. We have combinations with venetoclax that allow us to do time-limited therapy with all oral regimens like ibrutinib-venetoclax or acalabrutinib-venetoclax. There’s also now triplet regimens like the acalabrutinib-venetoclax-obinutuzumab regimen, as well as the standard-of-care venetoclax-obinutuzumab. We also still have continuous BTK inhibitor-based therapy with several agents approved, and so there’s lots of great options now for our patients. I’m excited about a couple of different areas right now in CLL research. I think one of the really promising classes of drugs that’s recently come about is the BTK degraders, which target BTK in a different way from the inhibitors and overcome some of the resistance mechanisms we can see with both covalent and non-covalent inhibitors. So I’m interested to see how BTK degraders first compare to the non-covalent inhibitor pirtobrutinib. We have some Phase III trials ongoing at that. But then also moving BTK degraders up into earlier lines of therapy, particularly as part of combination regimens and seeing how potent those can be. The other area I find very exciting is immune-based research, such as bispecific antibodies, as well as the CAR-T cell technologies that are in development. And so I’m excited to see where the future holds for those.
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