May 2019, not specific to CLL but adds to our understanding of CAR-T treatment. Extracted from a paper comparing neurological CRS grading assessments.
CRS is caused by the release of cytokines during in vivo CART cell expansion. The toxicity of CRS results from the systemic effects of cytokines on multiple organ systems.
Severe CRS causes toxicity beyond fever, hypotension responsive to fluids, and hypoxia responsive to low-level oxygen support. The likelihood of a patient experiencing severe CRS depends on patient-, tumor-, and CART-related factors.
In terms of patient-related factors, the baseline inflammatory state appears to be of particular importance, so patients with a high baseline serum ferritin, c-reactive protein, or elevated baseline cytokine levels are at a higher risk of CRS.
It appearsthat CRS is somewhat different depending on disease type and a higher tumor burden also appears to predict a higher rate of CRS.
The rate of CRS may also be modifiable by CART design or manufacturing practices, or may be different based on the costimulatory domain used (i.e., CD28 vs. 4-1BB).
Finally, earlier interventions with treatments such as corticosteroids and anti-interleukin 6 (IL-6) therapy (i.e., tocilizumab) appear to reduce the rates of severe CRS.
Jackie
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