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IBC 2025 | Investigating the long-term cytopenia observed after BCMA-targeted CAR-T therapy in multiple myeloma
Felipe Prósper, MD, PhD, University of Navarra, Pamplona, Spain, discusses a study investigating the long-term cytopenia observed after BCMA-targeted CAR T-cell therapy in multiple myeloma. This research identified specific cytokines and growth factors that hinder hematopoietic cell maturation, leading to the long-term myelotoxicity observed in some patients. By inhibiting these cytokines, normal hematopoiesis can be restored, providing potential clues for mitigating this side effect in patients receiving CAR-T therapy. This interview took place at the 3rd Intercepting Blood Cancers (IBC) Workshop held in Nice, France.
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Transcript
That was actually a nice idea that came up by talking to the clinicians, to my colleagues. We observed that after BCMA CAR T-cell therapies, you have a myelotoxicity that is significantly longer than what you observed after CD19 CARs. So trying, as the disease is mainly focused on the bone marrow, we try to understand whether there might be something related to the interaction between the CAR T-cells and the plasma cells that were interfering with normal hematopoiesis...
That was actually a nice idea that came up by talking to the clinicians, to my colleagues. We observed that after BCMA CAR T-cell therapies, you have a myelotoxicity that is significantly longer than what you observed after CD19 CARs. So trying, as the disease is mainly focused on the bone marrow, we try to understand whether there might be something related to the interaction between the CAR T-cells and the plasma cells that were interfering with normal hematopoiesis. So, with that hypothesis, we start working on trying to understand the differentiation from hematopoietic cells in the presence of supernatants, in the presence of some of the substances that are released when the bone marrow plasma cells interact with the CAR T-cells. And we identify some cytokines and growth factors produced after the interaction between the plasma cells and the CAR-Ts that were interfering with the normal maturation of hematopoiesis and that they may explain to some extent the long myelotoxicity that we observe in some patients. The interesting point of the study was actually that when we treat those cells with inhibitors of those cytokines, we can restore the normal hematopoiesis, at least providing some clues on how we could actually try to tackle this side effect in patients undergoing CAR T-cell therapies.
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