Neurological management and work-up of neurotoxicity associated with CAR T cell therapy

Neurological Research and Practice

Mike P. Wattjes¹  Matthias Eder²  Christian Koenecke²  Victoria Panagiota²  Arnold Ganser²  Christian Schultze-Florey²  Tabea Fröhlich²  Gernot Beutel²  Sascha David³  Günter Höglinger⁴  Nora Möhn⁴  Viktoria Bonda⁴  Lea Grote-Levi⁴  Sonja Körner⁴  Thomas Skripuletz⁴  Martin Stangel⁴ 

[1] Department of Diagnostic and Interventional Neuroradiology, Hannover Medical School;Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School;Department of Nephrology, Hannover Medical School;Department of Neurology, Hannover Medical School;

关键词: Autoimmunity;    Neurotoxicity;    Immunotherapy;    Chimeric Antigen Receptors;    T-Lymphocytes;   

DOI  :  10.1186/s42466-021-00166-5

来源: DOAJ

【 摘 要 】

Abstract Introduction Treatment with CD19 chimeric antigen receptor (CAR) T cells is an innovative therapeutic approach for patients with relapsed/refractory diffuse large B cell lymphoma (r/rDLBCL) and B-lineage acute lymphoblastic leukemia (r/rALL). However, convincing therapeutic response rates can be accompanied by cytokine release syndrome (CRS) and severe neurotoxicity termed immune effector cell-associated neurotoxicity syndrome (ICANS). Methods Single center, prospective observational study of fifteen consecutive r/r DLBCL patients treated with Tisagenlecleucel within 1 year at Hannover Medical School. Extensive neurological work-up prior to CAR T cell infusion included clinical examination, cognitive testing (Montreal-Cognitive-Assessment), brain MRI, electroencephalogram, electroneurography, and analysis of cerebrospinal fluid. After CAR T cell infusion, patients were neurologically examined for 10 consecutive days. Afterwards, all patients were assessed at least once a week. Results ICANS occurred in 4/15 patients (27%) within 6 days (4–6 days) after CAR T cell infusion. Patients with ICANS grade 2 (n = 3) exhibited similar neurological symptoms including apraxia, expressive aphasia, disorientation, and hallucinations, while brain MRI was inconspicuous in either case. Treatment with dexamethasone rapidly resolved the clinical symptoms in all three patients. Regarding baseline parameters prior to CAR T cell treatment, patients with and without ICANS did not differ. Conclusions In our cohort, ICANS occurred in only every fourth patient and rather low grade neurotoxicity was found during daily examination. Our results demonstrate that a structured neurological baseline examination and close monitoring are helpful to detect CAR T cell related neurotoxicity already at an early stage and to potentially prevent higher grade neurotoxicity.

【 授权许可】

Unknown