[Management of ICANS in Patient Treated with Anti-CD19 CAR T-Cell Therapy]

Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy has been established as a standard of care in selected patients with relapsed or refractory large B-cell lymphoma (LBCL). Unlike conventional cytotoxic chemotherapy, CAR T-cell therapy has unique immune-related adverse events, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Therefore, successful management of these toxicities are crucial for the safe and effective delivery of CAR T-cell therapy. In particular, severe ICANS can be associated with life-threatening complications and poor neurological outcomes. ICANS is thought to develop as a result of excessive cytokine production associated with CAR T-cell activation, as well as on-target/off-tumor effect of CD19 expression. Clinically, it presents with a broad spectrum of neurological manifestations, ranging from mild symptoms such as cognitive impairment and aphasia to severe manifestations including seizures, depressed level of consciousness, and cerebral edema. Because clinical findings are often nonspecific, the diagnosis of ICANS can be challenging. Nevertheless, given its potential for rapid progression, early recognition and careful monitoring are essential for optimal clinical management. With regard to treatment corticosteroids have been the mainstay of treatment for ICANS in Japan. Recently, however, prophylactic and therapeutic interventions using the interleukin-1 receptor antagonist, anakinra, have attracted attention as a novel treatment option, particularly in Western countries. In this review, we summarize the currently available data on ICANS associated with anti-CD19 CAR T-cell therapy, focusing on its pathophysiology, clinical features, diagnostic approach, and management strategies.