How I treat unique and difficult to manage cases of CAR T-cell therapy associated neurotoxicity.

With growing indications for Chimeric Antigen Receptor (CAR) T-cell therapy, toxicity profiles are evolving. There is an urgent and unmet need for approaches to optimally manage emerging adverse events that extend beyond the standard paradigm of cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS). While management guidelines exist for ICANS, there is little guidance on how to approach patients with neurologic comorbidities, and how to manage rare neurotoxicity presentations such as CAR T-cell therapy related cerebral edema, severe motor complications or late onset neurotoxicity. Here, we present three scenarios of patients treated with CAR T-cells who develop unique types of neurotoxicity, and we describe an approach to evaluation and management based on experience because objective data are limited. The goal of this manuscript is to develop awareness of emerging and unusual complications, discuss treatment approaches and help institutions and health care providers establish frameworks to navigate how to best address unusual neurotoxicities to ultimately improve patient outcomes.