Immune Effector Cell Associated Neurotoxicity (ICANS) Among Pediatric and AYA Patients: MD Anderson Cancer Center Experience

Abstract

Introduction Immune effector cell associated neurotoxicity (ICANS) and cytokine release syndrome (CRS) are unique potentially life-threatening complications associated with immune effector cell (IEC) therapies. ICANS presents with varying symptoms ranging from confusion to seizure and cerebral edema. There is no consensus on the precise pathophysiology related to ICANS. The incidence of this toxicity may vary based on the specific product, underlying diagnosis and host factors. Here, we characterize ICANS in pediatric and adult young adolescent (AYA) patients receiving IEC therapy at our institution. Methods We reviewed clinical characteristics, neurological severity and outcomes in pediatric and AYA patients who received IEC standard of care products from 2018-2019 at MDACC. Severity was retrospectively assessed based on ASTCT Consensus Criteria. Results Nine patients, median age 15.5 (range: 3-25) years received standard of care, chimeric antigen receptor (CART) IEC therapy. The primary diagnoses were pre-B cell acute lymphoblastic leukemia (ALL) (n=8) and primary mediastinal large B-cell lymphoma (n=1). Of these patients, 4 (44%) developed ICANS within a median of 8 (range: 3-27) days of CAR T cell infusion. ICANS was associated with CRS in all affected patients, occurring within a median of 6 (range: 2-7) days after CRS. Median CRS and ICANS severity grade was 2 (range 1-4) in all 9 patients. Symptoms included altered mental status (AMS) (5), seizure (1), aphasia (2), impaired ability to write a standard sentence (4). Neuroimaging did not correlate to ICANS symptoms or severity. EEG was obtained in 3 affected patients but only correlated to background slowing in one with aphasia. Lumbar puncture was performed in 2 patients with ICANS and was remarkable for lymphocytosis. All patients had received prophylactic anti-epileptic medication. All patients received tocilizumab for concomitant CRS and 3 received steroids. Conclusion Almost half of pediatric patients receiving standard of care CART products may experience ICANS within one week CAR T cell infusion that is associated with CRS. Pleocytosis in the CSF may be due to CAR-T trafficking into the CSF and prospective studies may clarify its significance. Impaired ability to write a standard sentence and the Cornell Assessment of Pediatric Delirium (CAPD) may be early indicators of ICANS in pediatric/AYA patients.