Immune effector cell-associated neurotoxicity syndrome (ICANS)

Today CAR-T-cell immunotherapy is the most advanced and promising treatment method in oncology and hematology. However, its implementation is associated with the development of severe adverse events. A significant neuropsychiatric complication associated with immunotherapy is immune effector cell-associated neurotoxicity syndrome (ICANS), previously referred to as cytokine release-induced encephalopathy syndrome (CRES). The clinical manifestations of ICANS are heterogeneous, including cerebral edema, mild lethargy, aphasia, seizures and others. A comprehensive diagnostic evaluation of ICANS includes electroencephalograms and neuroimaging studies. The incidence of ICANS varies depending on the specific CAR T-cell product used, with approximately 50 % of patients receiving CAR-T-cell therapy developing ICANS of varying severity, and severe cases (grades 3 and 4) occurring in about 25 % of patients. The treatment of ICANS is tailored based on its severity. In mild cases, such as stage 1, supportive therapy is generally sufficient and includes seizure prophylaxis and consultation with a neurologist. For more severe cases, beginning at stage 2, corticosteroids and interleukin activity inhibitors are employed. Seizures are managed using benzodiazepines and antiepileptic medications. This review provides up-to-date information on the pathogenesis, clinical neurological manifestations, risk factors, and therapeutic strategies for ICANS, and outlines the neurologist’s role in the diagnosis and management of this severe complication.