CAR T-cell therapy-related neurotoxicity in paediatric acute lymphocytic leukaemia.

ABSTRACT

BACKGROUND: The advent of chimeric antigen receptor (CAR) T-cell therapy has created a paradigm shift in the management of patients with refractory B-cell acute lymphocytic leukaemia (ALL). The aim of this study is to correlate imaging findings of CAR T-cell therapy related neurotoxicity with clinical course and eventual clinical outcome, with the hope that it will bring us a step closer to the identification of potential imaging biomarkers that may allow more accurate prognostication and risk stratification of patients. PROCEDURE Our imaging database was queried from January 2018 to April 2020 to identify paediatric patients who fulfil the following criteria (a) diagnosed with ALL, (b) underwent CAR T-cell therapy, and (c) had magnetic resonance imaging (MRI) brain studies performed before and after CAR T-cell therapy. A total of seven patients were included and all MRI studies were analysed by a paediatric neuroradiologist for the presence of acute neuroimaging findings post CAR T-cell infusion. Acute neuroimaging findings are defined as new imaging findings detected within 28 days of CAR T-cell infusion. RESULTS: Three out of four patients with acute neuroimaging findings had sustained complete remission for more than 6 months, while all three patients without acute neuroimaging findings had positive minimal residual disease (MRD) within 1 month. Both patients with acute diffuse leptomeningeal enhancement showed clinical improvement within 1-2 days. CONCLUSIONS: Acute neuroimaging findings may be a potential imaging biomarker for peak neurotoxicity and treatment response, and it is not necessarily associated with poor outcome, as previously reported.