Diabetes insipidus and Guillain-Barré-like syndrome following CAR-T cell therapy: a case report

BackgroundImmune effector cell-associated neurotoxicity syndrome (ICANS) is a common adverse event of CD19-directed chimeric antigen receptor (CAR) T cell therapy. Other neurological adverse events, however, have not methodically been described and studied. Furthermore, safety data on CAR-T cell the...

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Vydané v:	Journal for immunotherapy of cancer Ročník 11; číslo 1; s. e006059
Hlavní autori:	Koch, Christian, Fleischer, Juliane, Popov, Todor, Frontzek, Karl, Schreiner, Bettina, Roth, Patrick, Manz, Markus G., Unseld, Simone, Müller, Antonia M. S., Russkamp, Norman F.
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	England BMJ Publishing Group Ltd 01.01.2023 BMJ Publishing Group LTD BMJ Publishing Group
Predmet:	Antigens Blood cancer Cancer Case Report Case reports Cell- and Tissue-Based Therapy Cells Central Nervous System Neoplasms Cytokines Diabetes Diabetes Insipidus - etiology Diabetes Mellitus Dyspnea Guillain-Barre syndrome hematologic neoplasms Humans Hypothalamus Immunoglobulins Immunotherapy Immunotherapy, Adoptive - adverse effects Lymphocytes Lymphoma Lymphoma, Non-Hodgkin Nervous system Neurological disorders Neurotoxicity Ostomy Pathophysiology Pituitary gland Proteins Receptors, Chimeric Antigen Urine Ventilators hematologic neoplasms case reports receptors, chimeric antigen immunotherapy lymphoma
ISSN:	2051-1426, 2051-1426
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Shrnutí:	BackgroundImmune effector cell-associated neurotoxicity syndrome (ICANS) is a common adverse event of CD19-directed chimeric antigen receptor (CAR) T cell therapy. Other neurological adverse events, however, have not methodically been described and studied. Furthermore, safety data on CAR-T cell therapy in patients with central nervous system (CNS) lymphoma remain limited.Main bodyWe here report occurrence of a Guillain-Barré-like syndrome (GBS) and central diabetes insipidus (cDI) following tisagenlecleucel therapy for relapsed high-grade lymphoma with CNS involvement. Both complications were refractory to standard treatment of ICANS. Weakness of respiratory muscles required mechanical ventilation and tracheostomy while cDI was treated with desmopressin substitution for several weeks. Muscle-nerve biopsy and nerve conduction studies confirmed an axonal pattern of nerve damage. T cell-rich infiltrates and detection of the CAR transgene in muscle-nerve sections imply a direct or indirect role of CAR-T cell-mediated inflammation. In line with current treatment guidelines for GBS, intravenous immunoglobulin was administered and gradual but incomplete recovery was observed over the course of several months.ConclusionsThis case report highlights the risk of rare but severe neurological adverse events, such as acute GBS or cDI, in patients treated with CAR-T cells. It further underlines the importance of appropriate patient surveillance and systematic reporting of rare complications to eventually improve treatment.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 ObjectType-Report-3 ObjectType-Case Study-4 ObjectType-Case Study-2 ObjectType-Feature-4 content type line 23 ObjectType-Report-1 ObjectType-Article-3
ISSN:	2051-1426 2051-1426
DOI:	10.1136/jitc-2022-006059