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

Abstract

With growing indications for chimeric antigen receptor (CAR) T-cell therapy, toxicity profiles are evolving. There is an urgent and unmet need of approaches to optimally manage emerging adverse events that extend beyond the standard paradigm of cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome (ICANS). Although 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. In this study, we present 3 scenarios of patients treated with CAR T cells who develop unique types of neurotoxicity, and we describe an approach for the evaluation and management based on experience because objective data are limited. The goal of this study is to develop an 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.

Graphical abstract

Figure 1.

Examples of MRI changes during severe ICANS. Brain MRI during severe ICANS may rarely demonstrate symmetric T2/FLAIR hyperintensities in dorsal medial thalami (top; arrows) and tectal plate (bottom; arrowheads) resembling imaging changes associated with Wernicke encephalopathy. (A) MRI images from an adult patient with grade 4 ICANS. (B) MRI images from a pediatric patient with grade 4 ICANS. (C) Images from a pediatric patient with diffuse cerebral edema.