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iwCLL 2025 | The paradigm shift needed in CLL research and clinical trials
In this interview, Anna Schuh, MD, PhD, University of Oxford, Oxford, UK, comments on the paradigm shift she believes is necessary in chronic lymphocytic leukemia (CLL) research and clinical trials. Prof. Shuh emphasizes the need to focus on high-risk patients and to understand the underlying T-cell dysfunction of CLL, which drives the pathogenesis and risk of infection in this disease. This interview took place at the biennial International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2025 in Krakow, Poland.
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Transcript
Yeah, this has been a very interesting meeting for me in many ways. I’ve been thinking for quite some time in Oxford about what the next steps are in CLL management and how we can further improve on the brilliant progress that we’ve made in the last 20 years. And of course, the question of cure always comes up, and can we cure CLL? And certainly we’re at the point where we can achieve functional cure, so-called functional cure, in quite a few of our patients...
Yeah, this has been a very interesting meeting for me in many ways. I’ve been thinking for quite some time in Oxford about what the next steps are in CLL management and how we can further improve on the brilliant progress that we’ve made in the last 20 years. And of course, the question of cure always comes up, and can we cure CLL? And certainly we’re at the point where we can achieve functional cure, so-called functional cure, in quite a few of our patients. However, increasingly patients are saying, well, but we are still left with infectious complications. We have still got fatigue. All the numbers are telling us and the blood tests are telling us our disease is under control, but we don’t feel normal. We don’t feel that well. And we are worried about infections and the immune suppression.
So I have been thinking about this a little bit, and the data that we see at this meeting confirms really that the T-cell function plays a really important role in CLL, both in the pathogenesis of CLL itself, but then obviously also in the risk of infection. And the data we see now is that this T-cell dysfunction really occurs quite early on in the disease stage. And one of the approaches to potentially overcome T-cell dysfunction or prevent T-cell dysfunction from happening is to intervene more early. Of course, many studies or all studies so far have shown that that is not of clinical benefit. So we need to be very thoughtful in the way we are designing early intervention studies going forward in CLL. That includes very stringent selection of patients, focusing on very high-risk patients, but I think it also will include a component of making sure that the T-cells are reactivated or not damaged in the process of this early intervention.
So this is for me the really main focus, and I would hope that many clinical trials will be happening in the next few years looking at this relationship between the malignant B-cells and the T-cells that are clearly made dysfunctional and anergic by the leukemia.
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