Tandem Meetings 2023 | Incidence & management of HLH-like toxicities after CD19 CAR-T therapy

So what we did is we looked at all of our… so I think that CRS and ICANS are very well-defined, but there’s sort of this new phenomena that’s probably always been around that I think people might have labeled as severe CRS or hemophagocytic lymphohistiocytosis type syndrome. It probably doesn’t fit in any of those boxes perfectly because it’s a CAR-mediated toxicity, and so we looked at our experience with CAR T-cells, and we’ve had a lot of clinical experiences. I’ve been talking about with this 2019 construct, and we looked across multiple, sort of our institutional cohort of patients and found that there was a subset of patients that developed this HLH-like toxicity. It manifested again with this high ferritin coagulopathy, elevated liver enzymes, and generally correlated with worse outcomes. Many of these patients would end up dying of infectious complications because they needed additional immunosuppression to ameliorate this.

A lot of these patients got high doses of steroids or anakinra. Other people got ruxolitinib or other treatments available for this phenomena. So what we’re trying to do is just better define this. I think other groups have done the same and, really, with the goal of helping other institutions out there who may see toxicities like this to learn from our experience about how to manage it.

Our biggest takeaway is that it is reversible, and we’re actually treating it earlier rather than letting it continue on. Then, really, I think you have to be careful about mitigating infectious complications, which was really our major complication among patients who developed this HLH type syndrome.