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SOHO 2025 | Drivers of non-relapse mortality after CAR-T: cytopenias, infections & secondary malignancies
Kai Rejeski, MD, Ludwig-Maximilians University, Munich, Germany, shares insights into the current understanding of mortality drivers after CAR T-cell therapy, highlighting that the major causes of non-relapse mortality are cytopenias, immune deficits/infections, and secondary malignancies. Dr Rejeski emphasizes the need to improve reporting and grading of cytopenias and infectious complications, and further explains the importance of better understanding the link between CAR-T and the development of secondary malignancies. This interview took place at the 13th Annual Meeting of the Society of Hematologic Oncology (SOHO 2025) in Houston, TX.
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Transcript
So today I had the pleasure to talk a little bit about essentially our current understanding of what’s driving non-relapse mortality after CAR T-cell therapy. And so what I’d really try to highlight is the fact that as we have now gained more experience with CAR T-cell therapy, we’re understanding that these prototypical side effects of CAR T-cell therapy like CRS, like ICANS, like HLH, are actually not the major drivers of non-relapse mortality...
So today I had the pleasure to talk a little bit about essentially our current understanding of what’s driving non-relapse mortality after CAR T-cell therapy. And so what I’d really try to highlight is the fact that as we have now gained more experience with CAR T-cell therapy, we’re understanding that these prototypical side effects of CAR T-cell therapy like CRS, like ICANS, like HLH, are actually not the major drivers of non-relapse mortality. Instead, it’s side effects that are really known to hematologists for more than 70 years. It’s cytopenias, what we now term immune-effector cell-associated hemotoxicity, or ICAHT, it’s immune deficits and the associated infectious complications, and finally, it’s secondary malignancies. So I really tried to hone in on some of the unmet needs for each one of these. And so the first one for cytopenia is I think we’ve developed a grading system together with EHA and EBMT through the EHA-EBMT consensus grading for ICAHT. And it’s about implementing that now in clinical trials and also in registries, in international registries. For infectious complications, it’s all about reporting. So can we do a better job at really in detail describing the type of infection, the organism, Is it a bacterial, a viral, a fungal infection, the site of infection, if these infections occurred while the patients were on prophylactic agents, so if it’s a breakthrough infection or not. I think that’s where we really need to do a better job. And third, for secondary malignancies, it’s about understanding the mechanistic link between CAR T-cell therapy and the development of second primary malignancies. And I think that there, particularly for the myeloid malignancies, we have to understand what is the role that CAR-T-mediated inflammation is playing in the development of myeloid malignancies in particular.
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Disclosures
Kite/Gilead: Research Funding, Consultancy, Honoraria and travel support; Novartis: Honoraria; BMS/Celgene: Consultancy, Honoraria; Pierre-Fabre: travel support. CSL Behring: Consultancy
