Evidence for early, clinically silent medial temporal lobe inflammation after CAR-T cell therapy

Immune effector cell-associated neurotoxicity syndrome (ICANS) is the most frequent neurological complication following chimeric antigen receptor (CAR)-T cell therapy. Long-term cognitive effects remain controversial, even in the absence of clinical neurotoxicity. CAR-T cell-associated neurotoxicity often involves the medial temporal lobe (MTL), yet conventional structural magnetic resonance imaging (MRI) frequently remains normal. There is a need for markers of subclinical neurotoxicity that may predict long-term cognitive outcomes.

Therefore, we established an imaging protocol integrating 3 Tesla (T) and 7 T perfusion and functional connectivity MRI of the MTL in patients receiving CAR-T cells for B cell malignancies. Longitudinal data from four patients is presented here.

Two of the four patients developed ICANS (grade 1 and grade 3), and these patients also experienced mild cytokine release syndrome (CRS, grade 1). No structural abnormalities of the MTL were detected at baseline or during follow-up. CAR-T cell expansion varied markedly between patients. Regardless of ICANS, CRS, or CAR-T cell expansion, patients showed increased MTL perfusion and functional connectivity, most prominently at days 10-14.

These data suggest an early, clinically silent inflammatory response in the MTL with potential implications for long-term cognitive function, which requires further investigation.