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ASH 2025 | Observing late CAR T-cell re-expansion that does not result in malignant transformation
Fabian Müller, MD, University Hospital Erlangen, Erlangen, Germany, discusses the phenomenon of late re-expansion and high-level persistence of CAR T-cells that can be driven by single CAR+ T-cell clones without clinically evident CAR+ T-cell lymphoma. Dr Müller highlights that a comprehensive immune-monitoring approach at his institution has enabled the identification of stable T-cell clones with unusual phenotypes that persist over time without resulting in malignant transformation. This interview took place at the 67th ASH Annual Meeting and Exposition, held in Orlando, FL.
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Transcript
This is predominantly work by one of my coworkers who is like teaming up with me. He’s the head of the immune monitoring core at our clinic, so we do many things together. And he actually realized at one point that, or I have to start somewhere else. So different from many other centers, we are actually looking at the immune phenotype over time in all our patients...
This is predominantly work by one of my coworkers who is like teaming up with me. He’s the head of the immune monitoring core at our clinic, so we do many things together. And he actually realized at one point that, or I have to start somewhere else. So different from many other centers, we are actually looking at the immune phenotype over time in all our patients. So we have patients five years out after CAR-T, and we still collect their samples, and we look at, do they have CARs? What does the immune phenotype look like? So we do a relatively broad, and that’s expensive, that’s why many centers don’t do that. But we broadly look into their T-cell compartments all the time over many years. And we have patients, and that’s what this story is about, where you find very weird phenotypes of T-cells popping up over time, and the reasons for that are very diverse. We have a patient with infectious complications, very rare, actually a canine infection that this patient then had because of the immune suppression that the patient was suffering from, and we saw that by a T-cell change phenotypically. Other patients have that just by chance. And this is really important and interesting because currently we talk a lot about T-cell lymphoma after T-cell therapy and that there are certain alterations that we should be worried about. In those patients, we have stable T-cell clones that are oligoclonal or even monoclonal that are there for years, and they are just not changing. They’re just there. They look phenotypically weird, that’s why we got interested in them. And we are screening now our entire population, CAR-T-cell-treated population, to understand what the frequency is, where they come from, are they oligoclonal or not, sometimes infectious complications-associated, sometimes they are just there. We do CHIP analyses, right? So we wonder whether they do have a clonal hematopoiesis, like alteration. So that’s all super interesting. And I think for the field, it’s important to understand that not every oligo- or monoclonal T-cell population that comes up is immediately a T-cell lymphoma, which currently everybody publishes everywhere. But I think we have to think a little broader. And what we see is that several patients have alterations, but we would never consider them being malignant.
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