EBMT-EHA CAR-T 2019 | Dealing with CAR T-cell therapy neurotoxicity

Max Topp

Max Topp, MD University of Würzburg, Würzburg, Germany, discusses the importance of training for CAR T-cell therapy adverse events and the treatment given to those experiencing cytokine release syndrome. Prof. Topp speaks at the 1st European CAR T-Cell Meeting, held in Paris, France, co-organized by the European Society for Blood & Marrow Transplantation (EBMT) and the European Hematology Association (EHA).

Transcript (edited for clarity):

So I think the most important thing is that we have to be very well trained in detecting the early onset of these two adverse events. That’s done by training the physicians as well as the nursing staff. And then to follow algorithms, how to intervene very early onwards to prevent patients coming down with more severe forms of cytokine release syndrome or neurotoxicity.

For cytokine release syndrome, it is a combination of using predominantly dexamethasone with tocilizumab, a anti-IL-6 receptor antagonist in treating patients with cytokine release syndrome. And there’s an algorithm being developed that you use in the beginning of just one dose of tocilizumab and if cytokine release syndrome becomes more severe, grade two or grade three, then you give up to four doses. And also the amount of dexamethasone that you are to give to the patient is increased over time as the patient has more severe symptoms of cytokine release syndrome in that context.

The other one is that you have to work very closely to the ICU because at stage three, patients have to be transferred and so the ICU physicians have to know exactly what the symptoms are, how do you treat them and what is the best supportive care in that context.

I think the cytokine release syndrome that’s pretty straightforward what is causing it. It is the T-cells that are activated because there’s a very clear correlation between the severity of cytokine release syndrome and the initial expansion of the CAR T-cells in the patients. And as the T-cells are producing cytokines when they are activated, that makes a lot of sense that string. Yet, what we don’t understand is to which degree do other cells, other new cells contribute to the severity of cytokine release syndrome and B-cells, monocytes, macrophages, or granocytes in that context.

In terms of of neurotoxicity, I think there is a lot of evidence out there that it is caused also by cytokines. I think it’s highlighted by recent papers, last year, that IL-1 pathway seems to be very important and it is to be seen if blocking that pathway, so with IL-1 receptor agonists, if that going to help us to actually treat patients with severe neurotoxicity.

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