The Chronic Lymphocytic Leukemia Channel is supported with funding from AstraZeneca (Diamond), AbbVie (Platinum), Johnson & Johnson (Gold), BeOne Medicines (Silver) and Lilly (Silver).
VJHemOnc is an independent medical education platform. Supporters, including channel supporters, have no influence over the production of content. The levels of sponsorship listed are reflective of the amount of funding given to support the channel.
ESH CLL 2026 | Treatment strategies for CLL resistant to BTK inhibitors and venetoclax
Matthew Davids, MD, Dana-Farber Cancer Institute, Boston, MA, discusses treatment strategies for patients with chronic lymphocytic leukemia (CLL) who become resistant to both BTK inhibitors and venetoclax. He highlights the role of non-covalent BTK inhibitors such as pirtobrutinib as well as emerging approaches including CAR T-cell therapy and BTK degraders. This interview took place at the ESH CLL 2026 congress in Stockholm, Sweden.
These works are owned by Magdalen Medical Publishing (MMP) and are protected by copyright laws and treaties around the world. All rights are reserved.
Transcript
So when patients do become resistant to both covalent BTK inhibitors and BCL2 inhibitor venetoclax, this is a challenging population of patients to treat. One of the key distinctions is to understand whether these patients are so-called double exposed or double refractory. If they’re double exposed, meaning that perhaps they came off their covalent BTK inhibitor due to a toxicity, you may be able to try a different covalent BTK inhibitor and still get response and tolerability...
So when patients do become resistant to both covalent BTK inhibitors and BCL2 inhibitor venetoclax, this is a challenging population of patients to treat. One of the key distinctions is to understand whether these patients are so-called double exposed or double refractory. If they’re double exposed, meaning that perhaps they came off their covalent BTK inhibitor due to a toxicity, you may be able to try a different covalent BTK inhibitor and still get response and tolerability. However, if patients are truly double refractory to both mechanisms, then the main option now is a non-covalent BTK inhibitor, pirtobrutinib, which has a high overall response rate in the range of about 80% in that group. However, the PFS is only in the range of about a year and a half or a little bit less, and therefore we need new options for that population. We do have in the U.S. liso-cel, the CD19 CAR T-cell therapy approved, where we see about a 20% rate of complete response as monotherapy. And there’s very promising data now from BTK-degrader drugs in early phase clinical trials that look quite active in the double and even a triple refractory population.
This transcript is AI-generated. While we strive for accuracy, please verify this copy with the video.
Read more...
