ASTCT Consensus Grading for Toxicities after Immune Effector Cell Therapy.

Abstract

In 2019, the American Society for Transplantation and Cellular Therapy (ASTCT) developed consensus definitions and grading criteria for the common immune effector cell (IEC)-associated toxicities of cytokine release syndrome (CRS) and IEC-associated neurotoxicity syndrome (ICANS). These grading scales were widely adopted by clinicians, investigators, and sponsors, allowing a clearer understanding of outcomes across clinical trials and a uniform basis to inform treatment algorithms. Since then, other IEC class effects, such as IEC-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS) and non-ICANS attributable neurotoxicity, have been recognized. ASTCT convened experts for 2 tasks. First, to consider updating the previously published ASTCT grading criteria for CRS, ICANS, and IEC-HS. Second, to consider existing definitions and grading criteria, and/or create consensus criteria for emerging toxicities, including immune effector cell-associated hematotoxicity; non-ICANS neurological toxicities such as parkinsonism, cranial nerve palsies, and polyneuropathies; IEC-associated enterocolitis; tumor inflammation-associated neurotoxicity; and on-target, off-tumor toxicities. These updated consensus toxicity definitions and grading criteria can facilitate comparisons of toxicities of IEC and T-cell engager therapy across clinical trials and in real-world settings, as well as aid clinicians in better characterizing the severity of toxicity that can ultimately be tied to management guidelines.