iwNHL 2018 | Management of cytokine release syndrome and neurotoxicity: an emerging need

Bianca Santomasso

Bianca Santomasso, MD, PhD, of the Memorial Sloan Kettering Cancer Center, New York City, NY, discusses the manifestations and management of cytokine release syndrome and neurotoxicity, side effects of certain immunotherapies. Observations demonstrates the need for the development of more specific treatments for neurotoxicity, and while corticosteroids show some success in resolving the symptoms of neurotoxicity, an improved understanding of the pathophysiology and prevention of this conditions is still needed. This interview was recorded at the International Workshop on Non-Hodgkin Lymphoma (iwNHL) 2018 meeting, in Nice, France.

Transcript (edited for clarity):

I think, as a clinician, the first thing is that there are two main side effects from CAR-T cells: the first is Cytokine Release Syndrome and the second is neurotoxicity. It’s interesting because at first, people lumped the two together and thought they were the same entity and now it’s become more apparent that they’re probably two distinct entities; sometimes they can overlap a little bit in time, but neurotoxicity tends to happen after Cytokine Release Syndrome.

Maybe around the same time, but then it can also occur even after Cytokine Release Syndrome has resolved and the clinical manifestations can be diverse. It can be encephalopathy expressive aphasia, meaning difficulty in speaking, seizures, myoclonus or abnormal movements, hallucinations…So, it can be quite diverse and sometimes distressing for patients and families, so I think that many people have been trying to get a better understanding of it and how to manage it of course.

One thing that we learned is that some of the interventions that are used for Cytokine Release Syndrome in the United States, Tocilizumab, which is an anti-IL-6 receptor blocker, is FDA approved for the management of cytokine release syndrome. That doesn’t appear to help neurotoxicity, so currently we really just do supportive care and we use corticosteroids to try and tamp down the symptoms.

It’s unclear to me and others whether how much the steroids actually help reverse the process. Sometimes after steroids start it takes a few days for the neurotoxicity to resolve, but fortunately it does appear to resolve, and patients come through the process at the end recovered, so that much is fortunate, but I think we’re still trying to understand the pathophysiology and if there’s a way that we can even prevent it from occurring in the first place.

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