Investigational Biomarkers for Neurological Immune-related Adverse Events

Study Overview
=================
Brief Summary
-----------------
Neurological immune-related adverse events (n-irAEs) are an emerging group of disorders of patients with cancer treated with immune checkpoint inhibitors, presenting with heterogeneous clinical manifestations and of uncertain outcome. Novel genetic, inflammatory, and neurogenerative biomarkers could be associated with distinct phenotypes and different outcomes. To test this hypothesis, the study will provide: a phenotypic characterization and outcome assessment of patients with n-irAEs; the analysis of biomarkers of genetic predisposition (HLA and other immunity-related genes), inflammation (serum and cerebrospinal fluid [CSF] cytokines and autoantibodies, peripheral blood and CSF lymphocytes and other immune cells, neuroimaging), neurodegeneration (serum and CSF neurofilaments, neuroimaging) and their correlation with clinical features and outcome.

Official Title
-----------------
Genetic Predisposition, Inflammation, and Neurodegeneration Biomarkers in Patients With Neurological Adverse Events of Immune Checkpoint Inhibitors: Correlation With Clinical Phenotypes and Outcome

Conditions
-----------------
Neurological Disease

Intervention / Treatment
-----------------
* Genetic: Analysis of biomarkers and their correlation with clinical characteristics and outcome


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Clinical diagnosis of n-irAEs Exclusion Criteria: Presence of an alternative diagnosis explaining the neurological syndrome

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients with neurological immune-related adverse events (n-irAEs)<br>Patients developing neurological syndromes related to administration of any immune checkpoint inhibitors, including central nervous system disorders and neuromuscular toxicties | Genetic: Analysis of biomarkers and their correlation with clinical characteristics and outcome<br>* This is a non-interventional study involving clinical data, neuroimaging analysis, and biological samples. Demographics and clinical data are collected in the database of the French Reference Centre. Additional or missing data will be obtained by contacting the referral physicians. All the neuroimages available will be analysed by dedicated software. Samples are already stored in biobank repositories and collected as part of good clinical practice in the diagnostic process of patients with suspected autoimmune encephalitis, meaning that the standard diagnostic and therapeutic approaches will not be altered in the selected study population. Patients have already gave explicit written consent for biological specimens sampling and storage at the Centre de Ressources Biologiques des Hospices Civils de Lyon (CRB-HCL) (including tissue, cells or biological fluids). Additional samples for genetic testing will be collected upon explicit written consent.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Analysis of neurofilaments | Neurofilaments will be analysed by MSD. Meso Scale Discovery Electrochemiluminescence (MSD) uses sandwich enzyme-linked immunosorbent assay (ELISA) method coupled with electro¬chemiluminescence (ECL) detection and plate array technology to provide highly sensitive and multiplexed detection of the analytes of interest (like neurofilaments) in a complex biological matrix. | At enrollment | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Biomarkers, autoimmunity, immunotherapy side-effects, immune checkpoint inhibitors, neuroimmunology