Insights into neurological immune-related adverse events associated with immune checkpoint inhibitor cancer therapy — The Association Specialists
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Insights into neurological immune-related adverse events associated with immune checkpoint inhibitor cancer therapy (21764)

Magdalena Lerch 1 2 , Ming-Wei Lin 3 , David McDonald 3 , Markus Reindl 4 , Sarosh Irani 5 , David Brown 3 , Martin Stockler 6 7 , Matthew Cook 8 9 , Sudarshini Ramanathan 1 2 10
  1. Translational Neuroimmunology Group, Kids Neuroscience Centre, Children's Hospital at Westmead, Sydney, NSW, Australia
  2. Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
  3. NSW Health Pathology-ICPMR, Centre for Immunology and Allergy Research, Westmead Institute for Medical Research, University of Sydney, Sydney, NSW, Australia
  4. Clinical Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria
  5. Mayo Autoimmune Neurology Group, Department of Neurosciences, Mayo Clinic, Jacksonville, Florida, United States
  6. Department of Medical Oncology, Concord Cancer Centre, Concord Hospital, Sydney, NSW, Australia
  7. Department of Medical Oncology, Chris O’Brien Lifehouse, Sydney, NSW, Australia
  8. Division of Immunology and Infectious Diseases, John Curtin School of Medical Research, Australian National University and Canberra Clinical Genomics, Canberra, ACT, Australia
  9. Cambridge Institute of Therapeutic Immunology and Infectious Disease, Department of Medicine, University of Cambridge, Cambridge, United Kingdom
  10. Department of Neurology, Concord Hospital, Sydney, NSW, Australia

Aims: Cancer is a leading cause of morbidity and mortality worldwide. The development of immune checkpoint inhibitors (ICI) has revolutionised cancer therapy, and patients that were previously incurable can now have complete responses. However, their use can lead to the development of immune-related adverse events, which can induce severe disability, interruption of cancer therapy, and even death. Neurological autoimmune sequelae occur in 1-10% of patients treated with ICI and can be fatal. They can be associated with antibodies binding to neuronal or glial proteins. Here, we studied the presence of such autoantibodies in the serum of ICI-treated cancer patients, to define patients at risk and help with enabling a more personalised therapy. Methods: We analysed 169 serum samples of cancer patients before and after ICI treatment for the presence of neurological autoantibodies binding to nine different targets using gold standard live cell-based assays.Results: We found autoantibodies specific for multiple neuronal and glial targets in our ICI-treated cohort. Interestingly, while some patients developed these autoantibodies following ICI treatment, the majority of patients were already seropositive prior to ICI treatment initiation.Discussion: Our findings highlight the importance of testing for autoantibodies associated with neurological autoimmunity in cancer patients prior to receiving ICI. This can help with evaluating the individual risk for developing neurological immune-related adverse events associated with ICI, thereby creating a better personalised risk profile. Ultimately, a deeper understanding of the underlying immunological processes will contribute to minimising complications from ICI treatment and improving patient survival and quality of life.