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 | Emerging treatment strategies for Richter’s transformation in CLL
Barbara Eichhorst, MD, University Hospital Cologne, Cologne, Germany, discusses emerging treatment strategies for Richter’s transformation, highlighting promising results from the Phase II CLL-RT1 trial (NCT04271956) evaluating tislelizumab in combination with zanubrutinib. She also outlines the need for combination approaches and future options including CAR T-cell therapy and bispecific antibodies. 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
Patients with a Richter transformation still have a poor prognosis when they are treated with chemoimmunotherapy and due to their age cannot undergo consolidation therapy with allogenic stem cell transplantation. Therefore, luckily there are now numerous clinical trials out which are evaluating targeted combination therapies. Targeted treatments alone as covalent or non-covalent BTK inhibitors or checkpoint inhibitors aren’t very effective, so we have learned that we need combinations, doublets or even triplet combinations...
Patients with a Richter transformation still have a poor prognosis when they are treated with chemoimmunotherapy and due to their age cannot undergo consolidation therapy with allogenic stem cell transplantation. Therefore, luckily there are now numerous clinical trials out which are evaluating targeted combination therapies. Targeted treatments alone as covalent or non-covalent BTK inhibitors or checkpoint inhibitors aren’t very effective, so we have learned that we need combinations, doublets or even triplet combinations. Among the doublet combinations, there are data from the RT1 trial of the German CEL study group evaluating the checkpoint inhibitor tisotolizumab in combination with zanubrutinib. And in 48 patients, the overall response was 58%, median PFS 10.4 months. But what we do see is that we have long-term duration of remission in around one-third of the patients. And also after two years observation time, median overall survival has not yet been reached, and it looks even like a kind of plateau, but also due to the fact that some patients underwent allogenic stem cell transplantation. These are very promising data, and therefore we looked into detail which are the patients who respond to this treatment of checkpoint inhibitor plus zanubrutinib. And it seems that these are the patients whose Richter cells are carrying more an inflammatory type and responding more to the checkpoint inhibitors. And probably, therefore, we can develop a tool for prediction of response to these treatments. However, then two-thirds of the patients do not respond very well, we need additional treatment options in these patients, including immunotherapies with CAR T-cells or bispecific antibodies. The logic behind it is that monotherapy, either with kinase inhibitors or checkpoint inhibitors, is not effective enough. And that we also know with the kinase inhibitor, they rather have a more beneficial influence on T cells, on the immune function, rather improving immune function. And therefore, they’re a good partner to combine that with the checkpoint inhibitors. And yeah, as mentioned, that the combinations are necessary. If a doublet combination is enough or if we have to add something in addition, this will be further evaluated in clinical trials.
This transcript is AI-generated. While we strive for accuracy, please verify this copy with the video.
Read more...
