Non-ICANS NeurotoxiciƟes CD19-Directed CAR T-Cell Therapy and the Emergence of Movement and NeurocogniƟve Treatment-emergent Adverse Events (MNTs): A case report

Torsten Schroeder^1*Guranda Chitadze¹Justina Dargvainiene¹Tjark Martens¹Niklas Gebauer²Julia Frimmel¹Monika Brüggemann¹Thomas Valerius¹Natalie Schub¹Claudia D. Baldus¹Christiane Pott¹Frank Leypoldt¹Klarissa Hanja Stürner¹Friedrich Stölzel¹

• ¹Universitatsklinikum Schleswig-Holstein Campus Kiel, Kiel, Germany
• ²Department of Hematology and Oncology, University Hospital Schleswig-Holstein Lübeck, University of Lübeck, Germany, Lübeck, Germany

We report a 63-year-old male paƟent with diffuse large B-cell lymphoma (DLBCL) who developed delayed-onset neurotoxicity on day +22 following CD19-directed CAR T-cell therapy with axicabtagene ciloleucel (axi-cel), aŌer an iniƟal episode of CRS and ICANS. The underlying disease had relapsed with secondary central nervous system (CNS) involvement, highlighƟng a high-risk seƫng for neurotoxicity. Unlike classical ICANS, the syndrome featured progressive gait ataxia and hypokineƟc movement disturbances—clinical hallmarks of so-called movement and neurocogniƟve treatment-emergent adverse events (MNTs), a syndrome oŌen referred to as parkinsonism due to characterisƟc features such as bradykinesia, rigidity, tremor, and cogniƟve slowing. To date, such MNTs have only been reported in paƟents receiving BCMA-targeted CAR T-cell products, primarily for mulƟple myeloma. Our report is, to the best of our knowledge, the first documented case of an MNT-like syndrome following CD19-directed CAR T-cell therapy. The paƟent's symptoms evolved subacutely, in the absence of radiographic progression, infecƟon, or lymphoma relapse. Immunophenotyping revealed acƟvated effector-memory CD8⁺ T cells (HLA-DR⁺/CD38⁺/CD28⁻/PD1⁺) in peripheral blood, and predominantly CAR T cells in cerebrospinal fluid. Neurofilament light chain (NfL) levels rose significantly in serum and CSF, indicaƟng neuroaxonal injury. Steroid therapy led to parƟal clinical improvement. Follow-up neuropsychological tesƟng revealed persistent deficits in aƩenƟon and processing speed. This case broadens the known neurotoxicity spectrum of CAR T-cell therapies and underscores the need for heightened clinical vigilance and refined diagnosƟc criteria beyond ICANS, even in CD19-targeted seƫngs.