Neuroimaging findings in immune effector cell associated neurotoxicity syndrome after chimeric antigen receptor T-cell therapy

Abstract

Chimeric antigen receptor T-cell (CAR-T) therapy is a promising immunotherapy approved for hematological malignancies. Despite its effectiveness, clinically significant rates of toxicity, including immune effector cell associated neurotoxicity syndrome (ICANS), limit its widespread use. In certain contexts, ICANS may occur in up to one-third of patients using commercially available CAR-T therapies. The syndrome presents with a range of neurological signs and symptoms, as well as a variety of neuroimaging manifestations reported in the literature. A systematic review of the literature was performed. The systematic search strategy identified 24 studies discussing the neuroimaging appearances associated with ICANS. Imaging findings are more common in patients with higher grade neurotoxicity. The neuroimaging findings are heterogeneous, but can be grouped either anatomically (white matter, gray matter, brainstem, or leptomeninges) or pathologically (ischemic changes, hemorrhages, or cerebral edema). An understanding of the imaging manifestations of ICANS has the potential to impact the management of patients.

Keywords:

• Chimeric antigen receptor T-cell therapy
• hematological malignancies
• immune effector cell associated neurotoxicity syndrome
• neuroimaging
• magnetic resonance imaging

Disclosure statement

AHL: nil. MAA: nil. SJH: BMS/Celgene: consultancy, honoraria, advisory board, research funding, investigator on studies; GSK: consultancy, research funding, advisory board; Janssen Cilag: consultancy, honoraria, advisory board, research funding, investigator on studies; Novartis: consultancy, honoraria, advisory board, research funding, investigator on studies; Haemalogix: scientific advisory board, research funding, investigator on studies. MD: nil. TK: Tomas Kalincik has served on scientific advisory boards for BMS, Roche, Janssen, Sanofi Genzyme, Novartis, Merck, and Biogen, steering committee for Brain Atrophy Initiative by Sanofi Genzyme, received conference travel support and/or speaker honoraria from WebMD Global, Eisai, Novartis, Biogen, Sanofi-Genzyme, Teva, BioCSL, and Merck and received research or educational event support from Biogen, Novartis, Genzyme, Roche, Celgene, and Merck. AL: nil.

Additional information

Funding

Arian Lasocki was supported by a Peter MacCallum Cancer Foundation Discovery Partner Fellowship.