We determined clinical presentation, management, and outcome of patients with neurotoxicity after adoptive immunotherapy with chimeric antigen receptor (CAR) T-cells.

CAR T-cells have emerged as a promising class of cell-based immunotherapy in refractory malignancies. Neurotoxicity represents a common and potentially life-threatening adverse effect of CAR T-cell therapy, and clinical experience is limited.

A retrospective search of the institutional database of the Section of Neuro-Oncology at the Massachusetts General Hospital was performed. We identified patients who subsequently developed neurotoxicity after treatment with CAR T-cells. We collected demographic and clinical information; serum levels of acute phase reactants; electroencephalographic findings; treatment; use of steroids; and outcome.

25 patients treated with CAR T-cells for refractory or recurrent malignancies were identified. Twelve of the 25 patients (48%) had neurotoxicity grade 1-2 and thirteen patients (52%) had neurotoxicity grade 3-4. Median overall survival was 54.7 months. Eight patients (32%) with grade 3-4 neurotoxicity were deceased at database closure, while none died with neurotoxicity grade 1-2. We found that lower platelet counts at CAR T-cell infusion were associated with more severe neurotoxicity (p = 0.030). Cytokine release syndrome occurred in 24 out of 25 patients (96%). Serum levels of ferritin peaked with neurologic symptoms, and higher ferritin levels were associated with higher neurotoxicity grade. EEG showed patterns lying on the ictal-interictal continuum in most high-grade neurotoxicity patients. Grade 3-4 neurotoxicity correlated negatively with overall survival (p = 0.013). We did not find evidence that steroid use ≥7 days altered the patients’ overall survival when compared to <7 days of steroids (p = 0.808).

Randomized prospective studies of treatment algorithms are needed to improve patient monitoring and management. Blood biomarkers and EEG may be useful tools in optimizing patient care and will also need to be evaluated in future prospective clinical studies.