CAR-T Meeting 2025 | CAR T-cell-associated secondary malignancies: the need for more data and improved pharmacovigilance
Christian Buchholz, PhD, Paul-Ehrlich-Institut, Langen, Germany, discusses the occurrence of CAR T-cell-associated secondary malignancies, a treatment-related complication that presents a significant concern as more patients receive CAR-T. Prof. Buchholz highlights the need for a more thorough approach to pharmacovigilance to better understand when and in which patients these secondary malignancies arise. This interview took place at the EHA-EBMT 7th European CAR T-cell Meeting, held in Strasbourg, France.
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Transcript (AI-generated)
In gene therapy, of course, we have now a history of about 30 years and the field has had ups and downs. One of the biggest down events probably was the insertional oncogenesis that was observed in some children that had received at that time gamma retroviral vectors into the hematopoietic stem cells and then after a year or so developed leukemia, which was due to the insertion site of the retroviral vector close to transcription factors, which then resulted in a proliferative advantage of those hematopoietic stem cells and the malignancy...
In gene therapy, of course, we have now a history of about 30 years and the field has had ups and downs. One of the biggest down events probably was the insertional oncogenesis that was observed in some children that had received at that time gamma retroviral vectors into the hematopoietic stem cells and then after a year or so developed leukemia, which was due to the insertion site of the retroviral vector close to transcription factors, which then resulted in a proliferative advantage of those hematopoietic stem cells and the malignancy.
Nowadays we have much safer vectors, but still of course they integrate into the genome. With now 10,000 of patients that have received CAR T-cells, we are of course closely following whether any secondary malignancies are being reported from all those patients that have received CAR T-cells. And with now ongoing time and more patients being treated, these signals come up. There are more and more reports about secondary malignancies. But at the moment we don’t know yet if this is really associated with the retro or lentiviral vector that has integrated the CAR into the genome or if this is due to other effects like the conditioning, the background disease of the patient. There are various possibilities why there are secondary malignancies. And to find out we need data. Maybe a problem at the moment is that often the clinics and the physicians are not so much aware of this; they do not collect the material; they do not identify if really the CAR malignancies are CAR-positive. Things like that have to be done to, in the end, find out what is the reason for these malignancies and how to deal with it.
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