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SOHO 2026 | Understanding the risks of lymphoproliferative disorders following CAR T-cell therapy
Michael Jain, MD, PhD, Moffitt Cancer Center, Tampa, FL, shares insights into the spectrum of post-CAR T-cell therapy lymphoproliferative disorders, explaining that large-scale CAR T-cell proliferation in the blood and organs may drive delayed toxicities such as enterocolitis, cranial nerve palsies, and Parkinsonism. Dr Jain also notes the rare risk of malignant transformation into CAR T-cell lymphomas or leukemias, and highlights ongoing research into distinguishing and managing these complications. This interview took place at the 14th Annual Meeting of the Society of Hematologic Oncology (SOHO 2026) in Houston, TX.
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Transcript
One of the areas that has come out in CAR T cell therapy is when we see a really large number of CAR T-cells, either in the peripheral blood or inside of an organ. And this has most been seen in kind of the forefront with some of the myeloma CAR T’s like cilta-cel. And what we can see is sometimes these proliferations are occurring in the blood and they can be polyclonal or more often oligoclonal or even have aspects of clonality to them...
One of the areas that has come out in CAR T cell therapy is when we see a really large number of CAR T-cells, either in the peripheral blood or inside of an organ. And this has most been seen in kind of the forefront with some of the myeloma CAR T’s like cilta-cel. And what we can see is sometimes these proliferations are occurring in the blood and they can be polyclonal or more often oligoclonal or even have aspects of clonality to them. And we think that maybe these high proliferations that we see in the blood might end up subsequently causing toxicities a little bit later. And those toxicities may occur, for example, there’s an enterocolitis where we see some proliferations within the bowel. There are cranial nerve palsies where we think that there’s infiltration into the cranial nerves. Or a Parkinsonism where they may proliferate into the brain. The challenge is, you know, for example, if a patient has diarrhea, how do we know that it’s related to the CAR-T and not related to some other aspect of their care? And then when we go in and do a scope and maybe take a biopsy and we see all these lymphocytes, how do we know that they’re actually CAR T-cells? So specialized centers have set up to be able to see the CAR within the tissues, but it’s not a routine thing that’s going on everywhere. And then sometimes we worry, okay, occasionally maybe these proliferations actually represent a malignant event and these have turned into CAR T-cell lymphomas or CAR T-cell leukemias. It’s really rare, but we need to know about when that happens. And sometimes the lines are kind of blurred. You see these lymphocyte proliferations, they’re a bit clonal, and it’s very unclear what we should do in terms of their management. So I know that many groups are, there are ongoing publications, there’s new data that’s coming out, thinking about how to optimally distinguish these different situations, how to optimally manage these situations. But I think it’s a unique aspect of these T-cell therapies that we can see them clonally or oligoclonally expand. And we wonder how that’s relating to some of the problems that the patients may be experiencing.
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