Immune mediated neuropathy following checkpoint immunotherapy |
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| Affiliation: | 1. Department of Neurology, Royal North Shore Hospital, Sydney, NSW, Australia;2. Melanoma Institute of Australia, Sydney, NSW, Australia;3. The University of Sydney, Sydney, NSW, Australia;4. Department of Medical Oncology, Royal North Shore Hospital, Sydney, NSW, Australia;5. Department of Clinical Immunology and Allergy, Royal North Shore Hospital, Sydney, NSW, Australia;6. ImmunoRhuematology Laboratory, Pathology North, Sydney, NSW, Australia;1. Yale School of Medicine, New Haven, Connecticut; present affiliation at Harvard Radiation Oncology Program, Massachusetts General Hospital, Boston, Massachusetts;2. Department of Therapeutic Radiology, Yale School of Medicine, New Haven, Connecticut;3. Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, Connecticut;4. Department of Medicine, Yale School of Medicine, New Haven, Connecticut;6. Department of Neurosurgery, Yale School of Medicine, New Haven, Connecticut;1. Victorian Melanoma Service, Alfred Hospital, Melbourne, VIC, Australia;2. Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, Australia;3. Skin and Cancer Foundation Inc, Melbourne, VIC, Australia;4. Melanoma Institute Australia, The University of Sydney and Royal Prince Alfred Hospital, Sydney, NSW 2060, Australia;5. Melanoma Institute Australia, The University of Sydney and Royal North Shore Hospital, Sydney, NSW, Australia;1. Aix-Marseille University and APHM Hospital CHU Timone, Marseille, France;2. Melanoma Institute Australia, University of Sydney, and Mater Hospital, Sydney, NSW, Australia;3. University Hospital Essen and German Cancer Consortium, Essen, Germany;4. Massachusetts General Hospital Cancer Center, Boston, MA, USA;1. Division of Paediatric Neurology, Department of Paediatrics, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia;2. Biomedical Imaging Department, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia;3. Medical Imaging Unit, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh, Selangor, Malaysia;4. Division of Paediatric Infectious Diseases, Department of Paediatrics, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia;5. Division of Paediatric Intensive Care, Department of Paediatrics, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia;1. Melanoma Medical Oncology and Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;2. Service de Dermatologie Générale et Oncologique, Hôpital A Paré, Assistance Publique-Hôpitaux de Paris, Boulogne Billancourt, France;3. Melanoma Institute Australia, The University of Sydney, Royal North Shore and Mater Hospitals, Sydney, NSW, Australia |
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| Abstract: | Checkpoint immunotherapy has revolutionised cancer therapy and is now standard treatment for many malignancies including metastatic melanoma. Acute inflammatory neuropathies, often labelled as Guillain-Barre syndrome, are an uncommon but potentially severe complication of checkpoint immunotherapy with individual cases described but never characterised as a group. We describe a case of acute sensorimotor and autonomic neuropathy following a single dose of combination ipilimumab and nivolumab for metastatic melanoma. A literature search was performed, identifying 14 other cases of acute neuropathy following checkpoint immunotherapy, with the clinical, electrophysiological and laboratory features summarised. Most cases described an acute sensorimotor neuropathy (92%) with hyporeflexia (92%) that could occur from induction up till many weeks after the final dose of therapy. In contrast to Guillain-Barre syndrome, the cerebrospinal fluid (CSF) analysis often shows a lymphocytic picture (50%) and the electrophysiology showed an axonal pattern (55%). Treatment was variable and often in combination. 11 cases received steroid therapy with only 1 death within this group, whereas of the 4 patients who did not receive steroid therapy there were 3 deaths. In conclusion checkpoint immunotherapy – induced acute neuropathies are distinct from and progress differently to Guillain-Barre syndrome. As with other immunotherapy related adverse events corticosteroid therapy should be initiated in addition to usual therapy. |
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| Keywords: | Checkpoint immunotherapy CTLA-4, PD-1 Ipilimumab Nivolumab Neuropathy Guillain-Barre |
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