The Chronic Lymphocytic Leukemia Channel is supported with funding from AstraZeneca (Diamond), Johnson & Johnson (Gold) 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.
ERIC CLL 2026 | Which novel combinations hold promise for reshaping frontline and relapsed CLL?
Alexey Danilov, MD, PhD, City of Hope, Duarte, CA, discusses how novel combinations could reshape treatment for frontline and relapsed chronic lymphocytic leukemia (CLL), with a focus on time-limited therapies. Prof. Danilov emphasizes the importance of designing regimens that allow for treatment holidays and notes that combinations of BTK degraders, BTK inhibitors, and bispecific antibodies may be highly effective while mitigating risks. This interview took place at the 2026 ERIC International Meeting in Barcelona, Spain.
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
Yeah, I think the future is with time-limited therapy. We discussed that we have a colchicine-approved, zanubrutinib-sonrotoclax regimen is being investigated. So there are time-limited regimens with pirtobrutinib as well. The pirtobrutinib-venetoclax-rituximab has shown impressive efficacy in relapsed refractory CLL as well. And so I do think in frontline particularly, we should step away from continuous BTK inhibition or degradation for that matter and design regimens which allow for treatment holiday, which actually can be protracted in the majority, very protracted in the majority of patients...
Yeah, I think the future is with time-limited therapy. We discussed that we have a colchicine-approved, zanubrutinib-sonrotoclax regimen is being investigated. So there are time-limited regimens with pirtobrutinib as well. The pirtobrutinib-venetoclax-rituximab has shown impressive efficacy in relapsed refractory CLL as well. And so I do think in frontline particularly, we should step away from continuous BTK inhibition or degradation for that matter and design regimens which allow for treatment holiday, which actually can be protracted in the majority, very protracted in the majority of patients. So I do think if you think of BTK degraders, combinations with BCL2 inhibitors, whether it’s taca-dex-sonrotoclax or bexabrutideg-venetoclax, do have a future in both relapsed and frontline CLL and should be investigated. We talked about bispecifics. I do think the future is also with bispecifics, where bispecific antibodies in combination with venetoclax have shown very good efficacy in a European study recently. There is an ongoing study by Genmab, which will be results of which initial results will be reported soon. So I do think a combination, say, of BTK degraders, BTK inhibitors, and bispecific antibodies would be expected to be highly effective and mitigate some of the risks of bispecific antibodies, such as cytokine release syndrome. And finally, with CAR T-cells, now we believe that they do have better efficacy when you combine them with BTK inhibitors. And that may be due to the BTK inhibitor immunomodulatory effect, not even necessarily the effect on CLL cells, although that may still play a part, play a role by at least temporarily shutting down some immunosuppressive signaling emanating from CLL cells. But also the direct immunomodulatory effect of ibrutinib and potentially pirtobrutinib seems to help CAR T-cell efficacy. So I do think the future is with combinations in CLL.
This transcript is AI-generated. While we strive for accuracy, please verify this copy with the video.
Read more...
