Immunological Disorders and Immunotherapy
Open Access

Clinical Characteristics of Immune Effector Cell-Associated Neurotoxicity Syndrome

Faizuloev Evgeny^{* *}Correspondence: Faizuloev Evgeny, Department of Oncology, Complejo Hospitalario de Navarra-IdISNA, Pamplona, Spain, Email:

Author info »

Description

CAR-T cell therapy is an effective cancer treatment for several refractory/recurrent hematologic malignancies, but is associated with significant toxicities such as Immune Effector Cell- Associated Neurotoxic Syndrome (ICANS). Improved detection and assessment of ICANS could lead to improved management and expanded use of CAR-T cell therapy, but no objective specific biomarkers have been identified. We hypothesized that the severity of ICANS can be quantified from patterns of abnormal brain activity seen in ElectroEncephaloGram (EEG) signals. A retrospective observational study was performed in 120 patients receiving her CAR-T cell therapy who underwent electroencephalographic monitoring. Medical records were reviewed to determine each patient's daily her ICANS score. Using visually assessed EEG features and machine learning techniques, we created a Visual EEG Immune Effector Cellassociated Neurotoxic Syndrome (VE-ICANS) score and assessed the association between VE-ICANS and ICANS. It was also used to determine the importance and relative importance of EEG features.

Chimeric Antigen Receptor (CAR) T-cell therapy is a breakthrough treatment for relapsed and refractory malignancies with remission rates of up to 93% in patients with relapsed and refractory Acute Lymphoblastic Leukemia (ALL) Law. CAR-T cell therapy is also an effective treatment for Chronic Lymphocytic Leukemia (CLL) and Non-Hodgkin's Lymphoma (NHL), and has the potential to treat a wider range of cancers and autoimmune diseases. However, CAR-T cell therapies targeting CD19 and B-Cell Maturation Antigen (BCMA) can cause dangerous side effects such as Cytokine Release Syndrome (CRS) and Immune Effector Cell-associated Neurotoxic Syndrome (ICANS). ICANS is an acute side effect of her CAR-T cell therapy that occurs in 20%-70% of CAR-T patients and is characterized by altered mental status, headache, inattentiveness, aphasia, and possibly seizures, status epilepticus, and may manifest as drowsiness. An Intubation requires fulminant cerebral edema and is rarely fatal.

Treatment of ICANS is highly dependent on the physician's ability to accurately and timely diagnose ICANS and assess its severity. Steroids such as dexamethasone may be beneficial in treating his ICANS, but long-term exposure to steroids may reduce the desired effect of her CAR-T cell therapy on the underlying cancer. Tocilizumab, commonly used to treat Cytokine Release Syndrome (CRS), can also exacerbate ICANS. A reliable and readily available ICANS severity biomarker could improve our ability to manage these side effects, provide a costsaving tool, and improve patient outcomes.

Previous studies have suggested that ElectroencEphaloGraphy (EEG) may serve as a biomarker for ICANS due to changes in EEG patterns. A patient with ICANS exhibits significant EEG alterations such as delta and theta deceleration and Generalized Periodic Discharges (GPD), and the severity of these signs correlates with the severity of her ICANS symptoms. However, findings to date have been limited by small sample sizes and have not been widely used in clinical practice. EEG has proven itself as a biomarker for other disease states that present similar symptoms to ICANS. B. Delirium indicates promise. A delirium severity scale using qualitative EEG features successfully quantified the severity of delirium symptoms and the risk of adverse outcomes.

This study examines the importance of various qualitative (visually assessed) EEG features in ICANS and their correlation with ICANS severity. Traditionally written EEG reports are difficult to interpret by non-neurologists and often have no impact on clinical care beyond ruling out seizures. Therefore, we wanted to develop a data-driven approach for classifying EEG findings. We hypothesized that a grading system based on visually discernible features in a patient's EEG could provide an accurate and objective physiological measure of the severity of brain dysfunction in ICANS.