CAR-T Meeting 2023 | CAR-HLH: current management strategies and unmet needs
Muhammad Gohar Maqbool, MRCP (UK); MRCPE; FRACP; FRCPA, University Hospital Bristol NHS Foundation Trust, Bristol, UK, shares some insights into current approaches used to manage CAR-T cell-related hemophagocytic lymphohistiocytosis (CAR-HLH), including the use of anakinra, emapalumab and ruxolitinib, and the need for more research in this space. This interview took place at the EBMT-EHA 5th European CAR T-cell Meeting held in Rotterdam, The Netherlands.
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Transcript (edited for clarity)
The management, one of the key aspects, is managing the coagulopathy, which is associated with the hemophagocytic lymphohistiocytosis. And then because one of the key cytokine drivers is IL-1 beta and use of anakinra is warranted in these patients. If we get to use anakinra early, there might be a possibility to get the HLH under control rather quicker.
But then there are other cytokines, for example, interferon gamma, which is FDA, so there’s an FDA approved drug called emapalumab, which is used in primary refractory HLH, and it is thought to be one of the drivers associated with HLH in CAR-T cell therapy...
The management, one of the key aspects, is managing the coagulopathy, which is associated with the hemophagocytic lymphohistiocytosis. And then because one of the key cytokine drivers is IL-1 beta and use of anakinra is warranted in these patients. If we get to use anakinra early, there might be a possibility to get the HLH under control rather quicker.
But then there are other cytokines, for example, interferon gamma, which is FDA, so there’s an FDA approved drug called emapalumab, which is used in primary refractory HLH, and it is thought to be one of the drivers associated with HLH in CAR-T cell therapy. So there’s some potential to use this drug, although I do appreciate there are no currently available publications using this technique, but certainly it’s being used in primary refractory HLH. So there is some need, an unmet need, to probably utilize this drug.
And then another interesting drug is ruxolitinib. Ruxolitinib is a JAK inhibitor. And the cytokines, they do activate the JAK-STAT pathway because if you are able to innovate the JAK-STAT pathway by using ruxolitinib, there might be a possibility of controlling the hemophagocytic lymphohistiocytosis. Again, there are no sort of publications in the CAR-HLH setting, but in HLH in general, there is certainly a utility of ruxolitinib. So I think this is an area which will need to be explored for the management of CAR-HLH.
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