Use of Transcranial Doppler as a Biomarker of CAR T Cell–Related Neurotoxicity

Background and Objectives To examine the relationship between transcranial Doppler (TCD) mean flow velocity (MFV) and the severity and temporal onset of neurotoxicity after chimeric antigen receptor (CAR) T-cell therapy in patients with relapsed lymphoma. Methods We identified a cohort of 165 patients with relapsed or refractory B-cell lymphoma who received CAR T-cell therapy. TCDs were performed at baseline, treatment day 5, and throughout hospitalization based on development of neurologic symptoms. We assessed the percent change in velocity from baseline in each of the 6 major supratentorial arteries and the relationship of these values to development and timing of neurotoxicity. Results Our cohort was 30% female with an average age of 60 years. Of patients with TCDs performed, 63% developed neurotoxicity, and 32% had severe neurotoxicity. The median time of neurotoxicity onset was day 7. Higher maximum percent change in MFV across all vessels was significantly associated with likelihood of developing neurotoxicity (p = 0.0002) and associated with severe neurotoxicity (p = 0.0421). We found that with increased percent change in MFV, the strength of correlation between day of TCD velocity change and day of neurotoxicity onset increased. There was no single vessel in which increase in MFV was associated with neurotoxicity. Discussion Our study demonstrates an association between increase in TCD MFV and the development of neurotoxicity, as well as timing of neurotoxicity onset. We believe that TCD ultrasound may be used as a bedside functional biomarker in CAR T-cell patients and may guide immunologic interventions to manage toxicity in this complex patient group.