Managing cytokine release syndrome

ACP Immunotherapy Workshop

13 Oct 2017

Published: 18 Oct 2017

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Dr Charlotte Graham - King’s College London, London, UK

Dr Graham talks with ecancer at the ACP immunotherapy workshop about CRS, a side effect associated with recently approved CAR-T cell therapies.

She describes the presentation and pathways activated at the onset of cytokine release syndrome, and relates case details from one patient treated with tociluzumab and steroids.

I’m doing a case presentation on cytokine release syndrome which is a life-threatening complication of immunotherapy and particularly CAR T-cell therapy which is an emerging treatment for our patients.

What does this complication entail?

Patients initially develop fever and malaise, flu-like symptoms, but they can rapidly deteriorate with multi-organ failure requiring intensive care support. With the CAR T-cell therapy that’s being used up to 50% of patients end up in intensive care requiring organ support.

Why and how does it do this?

As the T-cells, these are genetically modified T-cells that recognise an antigen on the surface of cancer cells, as they come into contact with the antigen they become stimulated and activated and proliferate and they start secreting cytokines. These cytokines also signal to other immune cells within the patient such as macrophages and they secrete another cytokine, a chemical signal called IL-6, and this can contribute to this very extreme immune system over-activation and damage multiple organs.

How frequently does this occur?

It’s graded and a mild cytokine release syndrome we’ve seen almost universally in our patients but the more severe cytokine release syndrome requiring intensive care support is probably about 40%. But it varies between tumour type and between the type of CAR T-cell product being used.

Can you give some details about the specific case you are managing?

We work very closely with our intensive care colleagues and once this patient developed established cytokine release syndrome we gave him a drug called tocilizumab which is an IL-6 receptor blockade which has been used by a number of groups to treat cytokine release syndrome and has just been licensed by the FDA for severe cytokine release syndrome management. We also gave him some steroids which has a more global effect on immune cell secretion of cytokines.

Is there anything else important to mention from your talk?

In delivering these therapies you need to work very closely with other specialities and with intensive care because you really need them on board to help you deliver these treatments safely.