Cytokine Release Syndrome Following CD19 Directed Chimeric Antigen Receptor T-Cell Therapy

Chimeric antigen receptor (CAR) T-cell therapies have emerged as novel and promising treatments for hematologic malignancies. However, this new technology is associated with unique complications. Cytokine release syndrome (CRS) is a potentially severe side effect that can arise following infusion of CAR T-cells that consists of a systemic increase in proinflammatory cytokines, leading to serious toxicities. In this chapter, we discuss the rates of CRS that have been reported in clinical trials and real-world data, along with the predictive factors and biomarkers of CRS. We provide an overview of the pathogenesis of CRS, including the cytokines and cell-types that are drivers of this complication. We also discuss the diagnosis, grading, and management of CRS. Finally, we review secondary hemophagocytic lymphohistiocytosis and macrophage activation syndrome, a rare and serious adverse event following CAR T-cell therapy that is related, yet distinct from CRS. Overall, while the advent of CAR T-cell therapies as standard of care has initiated a paradigm shift in our treatment of hematologic diseases, understanding the underlying pathogenesis, diagnosis, and management of CRS will be critical for the continued and expanding use of these novel therapies.