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ESH CLL 2022 | CAR-T therapy vs BTK inhibitors in CLL treatment

In this video, Marco Ruella, MD, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, discusses the excitement surrounding the future use of chimeric antigen receptor T-cell (CAR-T) therapy in the treatment of chronic lymphocytic leukemia (CLL). While CLL treatment has largely been dominated by small molecules, Dr Ruella highlights the challenges of these therapies, and the potential transition into treatment with CAR-T products. Following this, Dr Ruella briefly mentions some results from a 10-year follow-up on two CLL patients who received CD19 CAR-T therapy and are still in remission. To conclude, Dr Ruella emphasizes the promise that CAR-T therapy is showing as a long-term treatment for CLL, and the need for more clinical trials and research in this area. This interview took place during the 2nd ESH Translational Research Conference on Chronic Lymphocytic Leukemia (ESH CLL), 2022.

Transcript (edited for clarity)

Of course, the landscape of treatments for CLL is dominated by small molecules, and for a good reason. They are very efficacious and they can maintain disease response for many years, so they’re certainly a great solution for many patients. However, what we know about long-term results of small molecules is that very few patients we can consider cured. So patients will have to continuously receive a drug for the rest of their life...

Of course, the landscape of treatments for CLL is dominated by small molecules, and for a good reason. They are very efficacious and they can maintain disease response for many years, so they’re certainly a great solution for many patients. However, what we know about long-term results of small molecules is that very few patients we can consider cured. So patients will have to continuously receive a drug for the rest of their life. And then the other thing is that there are certainly patients relapsing during this treatment, and importantly, there are patients that cannot tolerate this treatment, this oral small molecule. So the idea of having a CAR-T therapy that is working in CLL, of course it would be very exciting, because there could be the opportunity to have, in one shot, one cure. In other words, one infusion of these engineered T-cells that could potentially lead the patient to get a complete response and maintain the complete response in long-term, because as you know, these CAR-T cells can persist at long-term.

Let’s regard, for example, there was a recent publication by the group here at the University of Pennsylvania, Carl June and Jos Melenhorst showing 10-year follow-up of two patients that got CAR 19 for CLL, and they are still in remission now, and you can still detect CAR 19 cells in the blood of these patients. Just to tell you that it’s one infusion, but these CAR-T cells can persist in the long-term. So again, while more studies are needed to find the right product, the right combination for CLL, I do think that the opportunity to use CAR-T cells is very exciting, because it potentially can lead to long-term cures.

 

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