title: Neurological adverse events associated with immune checkpoint inhibitors: Review of the literature.
abstract: Immune checkpoint inhibitors (ICIs) targeting CTLA4 and PD1 constitute a promising class of cancer treatment but are associated with several immune-related disorders. We here review the literature reporting neurological adverse events (nAEs) associated with ICIs. A systematic search of literature, up to February 2016, mentioning nAEs in patients treated with ICIs was conducted. Eligible studies included case reports and prospective trials. One case seen in our ward was also added. Within the 59 clinical trials (totalling 9208 patients) analysed, the overall incidence of nAEs was 3.8% with anti-CTLA4 antibodies, 6.1% with anti-PD1 antibodies, and 12.0% with the combination of both. The clinical spectrum of neurological disorders was highly heterogeneous. Most of these nAEs were grade 1-2 and consisted of non-specific symptoms such as headache (55%). The incidence of high grade nAEs was below 1% for all types of treatment. Headaches, encephalopathies and meningitis were the most commonly reported (21%, 19% and 15%, respectively). Among the 27 case reports, the most common nAEs were encephalopathies, meningoradiculoneuritis, Guillain-Barré like syndromes and myasthenic syndromes. The median time of nAEs onset was 6 weeks. In most cases, drug interruption and steroids led to neurological recovery, even in conditions where steroids are not usually recommended such as Guillain-Barré syndrome.
authors.affiliation: Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Avicenne, Service de Neurologie, Bobigny, France; Université Paris 13, UFR de Santé, Médecine et Biologie Humaine, Bobigny, France. Electronic address: stefania.cuzzubbo@aphp.fr.
authors.forename: S
authors.initials: S
authors.lastname: Cuzzubbo
authors.affiliation: Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Avicenne, Service de Neurologie, Bobigny, France.
authors.forename: F
authors.initials: F
authors.lastname: Javeri
authors.affiliation: Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Avicenne, Service de Neurologie, Bobigny, France.
authors.forename: M
authors.initials: M
authors.lastname: Tissier
authors.affiliation: Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Avicenne, Service de Neurologie, Bobigny, France.
authors.forename: A
authors.initials: A
authors.lastname: Roumi
authors.affiliation: Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Avicenne, Service de Neurologie, Bobigny, France; Université Paris 13, UFR de Santé, Médecine et Biologie Humaine, Bobigny, France.
authors.forename: C
authors.initials: C
authors.lastname: Barlog
authors.affiliation: Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Avicenne, Service de Neurologie, Bobigny, France; Université Paris 13, UFR de Santé, Médecine et Biologie Humaine, Bobigny, France.
authors.forename: J
authors.initials: J
authors.lastname: Doridam
authors.affiliation: APHP Dermatology and CIC Departments, INSERM U976, Université Paris Diderot, Sorbonne Paris Cité, Hôpital Saint Louis, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Lebbe
authors.affiliation: Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Avicenne, Service de Neurologie, Bobigny, France; Université Paris 13, UFR de Santé, Médecine et Biologie Humaine, Bobigny, France.
authors.forename: C
authors.initials: C
authors.lastname: Belin
authors.affiliation: Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Avicenne, Service de Neurologie, Bobigny, France; Université Paris 13, UFR de Santé, Médecine et Biologie Humaine, Bobigny, France.
authors.forename: R
authors.initials: R
authors.lastname: Ursu
authors.affiliation: Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Avicenne, Service de Neurologie, Bobigny, France; Université Paris 13, UFR de Santé, Médecine et Biologie Humaine, Bobigny, France.
authors.forename: A F
authors.initials: AF
authors.lastname: Carpentier
mesh_terms: D000911:Antibodies, Monoclonal / Q000009:adverse effects*; D000970:Antineoplastic Agents / Q000009:adverse effects*; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors*; D006801:Humans; D007167:Immunotherapy / Q000009:adverse effects* / Q000379:methods; D015994:Incidence; D058990:Molecular Targeted Therapy / Q000009:adverse effects*; D009369:Neoplasms / Q000188:drug therapy*; D009422:Nervous System Diseases / Q000139:chemically induced* / Q000453:epidemiology; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors*
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D061026:Programmed Cell Death 1 Receptor
keywords: Anti-CTLA4; Anti-PD1; Immune checkpoint inhibitors; Neurological adverse events