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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2022-01-10

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

ABSTRACT

IntroductionTreatment 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).MethodsSingle 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.ResultsICANS 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.ConclusionsIn 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. More... »

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URI

http://scigraph.springernature.com/pub.10.1186/s42466-021-00166-5

DOI

http://dx.doi.org/10.1186/s42466-021-00166-5

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https://app.dimensions.ai/details/publication/pub.1144528249

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/35000613


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11 schema:description IntroductionTreatment 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).MethodsSingle 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.ResultsICANS 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.ConclusionsIn 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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17 schema:keywords B-cell lymphoma
18 B-lineage acute lymphoblastic leukemia
19 CAR T cells
20 CAR T-cell infusion
21 CAR T-cell therapy
22 CAR-T cell treatment
23 CD19 chimeric antigen receptor T cells
24 ConclusionsIn
25 DLBCL patients
26 Hannover Medical School
27 IntroductionTreatment
28 MRI
29 MethodsSingle-center
30 R DLBCL patients
31 T cells
32 T-cell infusion
33 T-cell therapy
34 T-cell treatment
35 acute lymphoblastic leukemia
36 analysis
37 antigen receptor T cells
38 aphasia
39 approach
40 apraxia
41 baseline examination
42 baseline parameters
43 brain MRI
44 cases
45 cell infusion
46 cell lymphoma
47 cell therapy
48 cell treatment
49 cells
50 center
51 cerebrospinal fluid
52 chimeric antigen receptor T cells
53 clinical examination
54 clinical symptoms
55 close monitoring
56 cognitive testing
57 cohort
58 consecutive days
59 cytokine release syndrome
60 daily examination
61 days
62 dexamethasone
63 diffuse large B-cell lymphoma
64 disorientation
65 early stages
66 electroencephalogram
67 electroneurography
68 examination
69 expressive aphasia
70 fluid
71 fourth patient
72 grade 2
73 grade neurotoxicity
74 hallucinations
75 high-grade neurotoxicity
76 immune effector cell-associated neurotoxicity syndrome
77 infusion
78 innovative therapeutic approaches
79 large B-cell lymphoma
80 leukemia
81 lymphoblastic leukemia
82 lymphoma
83 management
84 medical schools
85 monitoring
86 neurological management
87 neurological symptoms
88 neurotoxicity
89 neurotoxicity syndrome
90 observational study
91 parameters
92 patients
93 prospective observational study
94 rate
95 receptor T cells
96 refractory diffuse large B-cell lymphoma
97 release syndrome
98 response rate
99 results
100 schools
101 severe neurotoxicity
102 similar neurological symptoms
103 stage
104 study
105 symptoms
106 syndrome
107 testing
108 therapeutic approaches
109 therapeutic response rate
110 therapy
111 tisagenlecleucel
112 treatment
113 weeks
114 years
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