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01-12-2022 | Cranial MRI | Research article

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

Authors: Nora Möhn, Viktoria Bonda, Lea Grote-Levi, Victoria Panagiota, Tabea Fröhlich, Christian Schultze-Florey, Mike P. Wattjes, Gernot Beutel, Matthias Eder, Sascha David, Sonja Körner, Günter Höglinger, Martin Stangel, Arnold Ganser, Christian Koenecke, Thomas Skripuletz

Published in: Neurological Research and Practice | Issue 1/2022

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.

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Title: Neurological management and work-up of neurotoxicity associated with CAR T cell therapy
Authors: Nora Möhn
Viktoria Bonda
Lea Grote-Levi
Victoria Panagiota
Tabea Fröhlich
Christian Schultze-Florey
Mike P. Wattjes
Gernot Beutel
Matthias Eder
Sascha David
Sonja Körner
Günter Höglinger
Martin Stangel
Arnold Ganser
Christian Koenecke
Thomas Skripuletz
Publication date: 01-12-2022
Publisher: BioMed Central
Keywords: Cranial MRI
Electroencephalography
CAR T-Cell Therapy
Apraxia
Published in: Neurological Research and Practice / Issue 1/2022
Electronic ISSN: 2524-3489
DOI: https://doi.org/10.1186/s42466-021-00166-5

Keynote webinar | Spotlight on medication adherence

Springer Medicine

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

Abstract

Introduction

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Introduction

Methods

Results

Conclusions

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