CAR-T Meeting 2026 | The current status of CAR T-cell therapy in CLL

The last years have transformed completely the landscape of treatment of CLL and we have a lot of targeted therapies that mainly comprise the whole CLL treatment landscape nowadays. However, we still have patients that particularly after Bruton’s tyrosine kinase inhibitors or BCL2 inhibitors do either, well, are exposed to those substances and eventually relapse or that do not respond to treatment. So we have the double exposed or double refractory group of patients that are in need of further treatment options. And we have CAR T-cells available in the U.S. by the FDA. However, in Europe, we do not have CAR T-cells for CLL available – that’s purely an academic field where Spain has had their products available in the academic fields, and since September of 2025, we in Germany at the Heidelberg University Hospital also have one product to treat our patients with CAR T-cell treatment after failure of BTK and BCL2 therapy. 

We are mainly concentrating on CD19 as the target that is for a liso-cel, which is approved in the US. This is also true for the products that we have in Spain or in Germany. They all target CD19 as the main target on B-cell development. It’s expressed, with exception of the stem cell, on almost all developing stages of the B-cell and therefore is a promising, well, is the target, still the main target. We have approved products only for CD19 and BCMA, BCMA being restricted to the very mature B-cell, the plasma cells, in the context of myeloma. So it’s still CD19 that it’s addressed. 

For the target population that I talked about, well, those BTK and BCL2 inhibitor-failing patients, we need a cellular therapy. We’ve had allogeneic stem cell transplantation, and we still have it, obviously. However, morbidity and mortality of allogeneic stem cell transplantation with GVHD and everything is high. With CAR-T, we have an option of treatment. We know, however, that CAR-T in CLL is limited by the manufacturing problems that we face, that it was one point. And the second point is that we have a high correlation of efficacy with tumor burden. That means that in CLL particularly, the amount of malignant cells determines a little bit of the outcome to CAR T-cells. The lesser the better, I think you would say, I hope it’s correct. And that is something that, although we see it for the other entities in CAR T-cell treatment also, it’s still a very particular point that has to be addressed when we treat CLL patients with CAR T-cells. We had the experience of brexucabtagene autoleucel, ZUMA-8, where 15 patients were evaluated and only those patients with low tumor burden responded. We have also data on liso-cel in patients where also the correlation of efficacy with tumor or low tumor burden has been shown. And that means that we have kind of, with manufacturing difficulties of exhausted T-cells in another T-cell compartment to produce autologous CAR T-cells in those patients, we have kind of a little bit different situation than for other entities. So, yes, there is an efficacy. Maybe it will be also in combination as or as bridging to allogeneic stem cell transplantation. We have to see that. However, what we see in the real-world data presented at ASH last year on liso-cel in 41 patients, we see that the bridging and bridging particular with the non-covalent BTKis can significantly improve outcome of patients with CAR-T in CLL.

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