Abstracts

Rationale: Chimeric antigen receptor (CAR) T cells are used as treatment for relapsed and refractory hematologic malignancies. Unfortunately, treatment can be complicated by acute neurotoxicity of varying grades. While the pathophysiology of neurotoxicity with CAR T therapy remains to be elucidated, even less is known about how to predict which patients will go on to develop neurotoxicity. This retrospective study investigated if pre-CAR T therapy EEGs could be used to predict the development of neurotoxicity and if there is a correlation between EEG changes and the degree of neurotoxicity.

Methods: We retrospectively reviewed patients who were treated with CAR T-cells between October 2020 and December 2021 at Moffitt Cancer Center Florida. Data were collected through chart review. Prior to CAR T-cell therapy, patients were seen in neurology clinic and baseline EEG was performed. During CAR-T cell therapy, neurotoxicity was assessed daily, and grading of immune effector cell-associated neurotoxicity syndrome (ICANS) was performed by the inpatient provider. Further EEGs were obtained upon clinician request, generally if the patient showed signs of neurotoxicity. Correlation between ICANS grades and EEG slowing was evaluated by linear regressions. Data analysis was performed using Stata 15.

Results: We identified 91 patients, 89 of which had lymphomas and 2 had acute leukemia. Forty-four patients did not develop any neurotoxicity, 16 patients had ICANS grade one, 8 patients had ICANS grade two, 19 patients had ICANS grade three and 4 patients had ICANS grade four. Two patients had a prior history of epilepsy. There were no clinical events concerning for seizures in any patient._x000D_
Regarding baseline EEGs prior to CAR T-cell therapy, 73 patients had baseline EEGs performed, and of these, 70 EEGs were interpreted as normal with a posterior dominant rhythm (PDR) in the alpha range. A normal baseline EEG did not have any predictive value on the future outcome of neurotoxicity (mean ICANS grade, 1.1 ± 1.28 SD).
_x000D_ Twenty-eight patients had inpatient EEGs following CAR T-cell therapy.  The PDR was in the alpha range for 4 patients and was in the theta range in 24 patients. A slower PDR frequency was significantly correlated with a higher ICANS grade (P < 0.001) (Figure 1)._x000D_
Twenty-four patients had both a baseline EEG and an EEG after development of CAR T-cell therapy associated neurotoxicity. The delta PDR was defined as the frequency of the baseline PDR minus the PDR frequency of the following EEG. A higher change in delta PDR was significantly correlated with a higher ICANS grade (P=0.001) (Figure 2).

Conclusions: In conclusion, a normal pre-CAR T EEG did not correlate with the future development of neurotoxicity. However, EEG abnormalities captured while a patient was experiencing neurotoxicity, and particularly a greater change from baseline PDR, was significantly correlated with a greater degree of neurotoxicity.

Funding: None