Clinical and radiologic correlates of neurotoxicity after axicabtagene ciloleucel in large B-cell lymphoma

Neurotoxicity or immune effector cell-associated neurotoxicity syndrome (ICANS) is the second most common acute toxicity after chimeric antigen receptor (CAR) T-cell therapy. However, there are limited data on the clinical and radiologic correlates of ICANS. We conducted a cohort analysis of 100 consecutive patients with relapsed or refractory large B-cell lymphoma (LBCL) treated with standard of care axicabtagene ciloleucel (axi-cel). ICANS was graded according to an objective grading system. Neuroimaging studies and electroencephalograms (EEGs) were reviewed by an expert neuroradiologist and neurologist. Of 100 patients included in the study, 68 (68%) developed ICANS of any grade and 41 (41%) had grade $3. Median time to ICANS onset was 5 days, and median duration was 6 days. ICANS grade $3 was associated with high peak ferritin (P 5 .03) and C-reactive protein (P 5 .001) levels and a low peak monocyte count (P 5 .001) within the 30 days after axi-cel infusion. Magnetic resonance imaging was performed in 38 patients with ICANS and revealed 4 imaging patterns with features of encephalitis (n 5 7), stroke (n 5 3), leptomeningeal disease (n 5 2), and posterior reversible encephalopathy syndrome (n 5 2). Abnormalities noted on EEG included diffuse slowing (n 5 49), epileptiform discharges (n 5 6), and nonconvulsive status epilepticus (n 5 8). Although reversible, grade $3 ICANS was associated with significantly shorter progression-free (P 5 .02) and overall survival (progression being the most common cause of death; P 5 .001). Our results suggest that imaging and EEG abnormalities are common in patients with ICANS, and high-grade ICANS is associated with worse outcome after CAR T-cell therapy in LBCL patients.