Rules of the road

Why early management of CRS may cut CAR T toxicity without denting efficacy

Investigators and companies have long been devising strategies to mitigate or preempt toxicities from CAR T cell therapies without compromising efficacy. Now, data presented at the American Society of Hematology meeting suggest strategies to prevent or reduce cytokine release syndrome are on the right track, and could even be taken further.

More work needs to be done to understand the causes of and solutions for neurological toxicities, especially in light of reports of cerebral edema in trials of Juno Therapeutics Inc.’s JCAR015.

Cytokine release syndrome (CRS) has occurred to some degree in most if not all CAR T studies.

CRS, a group of inflammatory symptoms caused by elevated cytokine levels, is the primary toxicity of CAR T cell proliferation. Milder manifestations of CRS may produce flu-like symptoms, but when more severe it can cause capillary leak, hypotension, organ failure and death.

Early on, researchers discovered that high levels of IL-6 occur frequently during CRS and that blocking the cytokine’s receptor using Roche’s Actemra tocilizumab can quickly improve symptoms, as can steroids that act as a broader check on inflammation.

However, T cell

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