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ERIC CLL 2026 | Exploring CAR-T and bispecifics in CLL: novel approaches beyond BTK and BCL2 inhibitors
Alexey Danilov, MD, PhD, City of Hope, Duarte, CA, discusses novel approaches for patients with chronic lymphocytic leukemia (CLL) who have exhausted BTK and BCL2 inhibitors, highlighting the potential of cell therapy, such as CAR-T, and bispecific antibodies. Prof. Danilov notes that while CAR T-cells are promising, access is limited, and bispecifics offer an easier, off-the-shelf alternative, with several agents in development, including epcoritamab, mosunetuzumab, and surovatamig. This interview took place at the 2026 ERIC International Meeting in Barcelona, Spain.
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Transcript
Yeah, so we do have cell therapy approved in CLL for patients who are refractory to BTK inhibitors, BCL2 inhibitors. Liso-cel has been studied alone and in combination with BTK inhibitors. A recent real-world analysis suggests that the responses to liso-cel may actually be somewhat better than what we have seen in initial studies. Of course, it’s an expensive treatment, which is still quite cumbersome and requires quite a lot of logistical preparation...
Yeah, so we do have cell therapy approved in CLL for patients who are refractory to BTK inhibitors, BCL2 inhibitors. Liso-cel has been studied alone and in combination with BTK inhibitors. A recent real-world analysis suggests that the responses to liso-cel may actually be somewhat better than what we have seen in initial studies. Of course, it’s an expensive treatment, which is still quite cumbersome and requires quite a lot of logistical preparation. But nevertheless, I do think patients who are progressing on BCL2 and BTK inhibitors need to be considered for CAR T-cells. The majority of patients will be candidates. I would say there are not that many patients who are poor candidates for CAR-T as the treatment is overall quite well tolerated. However, it’s not available in all regions. It’s not. Certainly, even in the United States, access to CAR-T is limited, even not just for CLL patients, but for non-Hodgkin lymphoma patients as well. You know, bispecifics are being developed at a rampant pace in non-Hodgkin lymphoma. There are frontline studies reading out which show high efficacy of bispecific CD20-CD3 targeting antibodies in frontline DLBCL, for example. And we have shown high efficacy of epcoritamab, a CD20-CD3 targeting bispecific antibody, in relapsed/refractory CLL in patients who are heavily pretreated, and it’s an easy off-the-shelf drug. So I actually would like to see more development of bispecifics in CLL. So that includes epcoritamab and mosunetuzumab, which I know is in clinical trials. There is also a CD19, CD3 targeting bispecific from AstraZeneca, surovatamig which also will be entering clinical studies in CLL. So cell therapy, T-cell engaging therapies are a very good choice for patients who are failing targeted therapies. And I think those might also move into earlier lines of therapy as we learn how to use them better.
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