Diabetes insipidus and Guillain-Barré-like syndrome following CAR-T cell therapy: a case report
Background Immune 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 th...
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BMJ Publishing Group
2023-01-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/11/1/e006059.full |
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| author | Christian Koch Patrick Roth Juliane Fleischer Todor Popov Karl Frontzek Bettina Schreiner Markus G. Manz Simone Unseld Antonia M. S. Müller Norman F. Russkamp |
| author_facet | Christian Koch Patrick Roth Juliane Fleischer Todor Popov Karl Frontzek Bettina Schreiner Markus G. Manz Simone Unseld Antonia M. S. Müller Norman F. Russkamp |
| author_sort | Christian Koch |
| collection | DOAJ |
| description | Background Immune 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 body We 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.Conclusions This 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. |
| format | Article |
| id | doaj-art-a2020bdc501145f7a8e17396c48a49e8 |
| institution | Kabale University |
| issn | 2051-1426 |
| language | English |
| publishDate | 2023-01-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-a2020bdc501145f7a8e17396c48a49e82025-01-29T11:25:09ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262023-01-0111110.1136/jitc-2022-006059Diabetes insipidus and Guillain-Barré-like syndrome following CAR-T cell therapy: a case reportChristian Koch0Patrick Roth1Juliane Fleischer2Todor Popov3Karl Frontzek4Bettina Schreiner5Markus G. Manz6Simone Unseld7Antonia M. S. Müller8Norman F. Russkamp91 Department of Medical Oncology and Hematology, University Hospital Zurich and University of Zurich, Zurich, Switzerland3 Department of Neurology, University Hospital and University of Zurich, Zurich, Switzerland2 Institute of Intensive Care Medicine, University Hospital Zurich, Zurich, Switzerland3 Department of Neurology, University Hospital and University of Zurich, Zurich, Switzerland4 Institute of Neuropathology, University Hospital and University of Zurich, Zurich, Switzerland3 Department of Neurology, University Hospital and University of Zurich, Zurich, SwitzerlandDepartment of Medical Oncology and Hematology, University Hospital Zurich, Zurich, Switzerland2 Institute of Intensive Care Medicine, University Hospital Zurich, Zurich, Switzerland5 Department of Transfusion Medicine and Cell Therapy, Medical University Vienna, Vienna, Austria1 Department of Medical Oncology and Hematology, University Hospital Zurich and University of Zurich, Zurich, SwitzerlandBackground Immune 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 body We 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.Conclusions This 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.https://jitc.bmj.com/content/11/1/e006059.full |
| spellingShingle | Christian Koch Patrick Roth Juliane Fleischer Todor Popov Karl Frontzek Bettina Schreiner Markus G. Manz Simone Unseld Antonia M. S. Müller Norman F. Russkamp Diabetes insipidus and Guillain-Barré-like syndrome following CAR-T cell therapy: a case report Journal for ImmunoTherapy of Cancer |
| title | Diabetes insipidus and Guillain-Barré-like syndrome following CAR-T cell therapy: a case report |
| title_full | Diabetes insipidus and Guillain-Barré-like syndrome following CAR-T cell therapy: a case report |
| title_fullStr | Diabetes insipidus and Guillain-Barré-like syndrome following CAR-T cell therapy: a case report |
| title_full_unstemmed | Diabetes insipidus and Guillain-Barré-like syndrome following CAR-T cell therapy: a case report |
| title_short | Diabetes insipidus and Guillain-Barré-like syndrome following CAR-T cell therapy: a case report |
| title_sort | diabetes insipidus and guillain barre like syndrome following car t cell therapy a case report |
| url | https://jitc.bmj.com/content/11/1/e006059.full |
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