Increased frequency of anti-Ma2 encephalitis associated with immune checkpoint inhibitors.
Aged
Antibodies, Monoclonal, Humanized
/ adverse effects
Antigens, Neoplasm
/ immunology
Antineoplastic Agents, Immunological
/ adverse effects
Encephalitis
/ chemically induced
Humans
Immunologic Factors
/ adverse effects
Ipilimumab
/ adverse effects
Male
Middle Aged
Neoplasms
/ drug therapy
Nerve Tissue Proteins
/ immunology
Nivolumab
/ adverse effects
Paraneoplastic Syndromes, Nervous System
/ chemically induced
Retrospective Studies
Journal
Neurology(R) neuroimmunology & neuroinflammation
ISSN: 2332-7812
Titre abrégé: Neurol Neuroimmunol Neuroinflamm
Pays: United States
ID NLM: 101636388
Informations de publication
Date de publication:
11 2019
11 2019
Historique:
received:
24
04
2019
accepted:
08
07
2019
entrez:
28
8
2019
pubmed:
28
8
2019
medline:
2
10
2020
Statut:
epublish
Résumé
To report the induction of anti-Ma2 antibody-associated paraneoplastic neurologic syndrome (Ma2-PNS) in 6 patients after treatment with immune checkpoint inhibitors (ICIs). We also analyzed (1) patient clinical features compared with a cohort of 44 patients who developed Ma2-PNS without receiving ICI treatment and (2) the frequency of neuronal antibody detection before and after ICI implementation. Retrospective nationwide study of all patients with Ma2-PNS developed during ICI treatment between 2017 and 2018. Our series of patients included 5 men and 1 woman (median age, 63 years). The patients were receiving nivolumab (n = 3), pembrolizumab (n = 2), or a combination of nivolumab and ipilimumab (n = 1) for treatment of neoplasms that included lung (n = 4) and kidney (n = 1) cancers and pleural mesothelioma (n = 1). Clinical syndromes comprised a combination of limbic encephalitis and diencephalitis (n = 3), isolated limbic encephalitis (n = 2), and a syndrome characterized by ophthalmoplegia and head drop (n = 1). No significant clinical difference was observed between our 6 patients and the overall cohort of Ma2-PNS cases. Post-ICI Ma2-PNS accounted for 35% of the total 17 Ma2-PNS diagnosed in our center over the 2017-2018 biennium. Eight cases had been detected in the preceding biennium 2015-2016, corresponding to a 112% increase of Ma2-PNS frequency since the implementation of ICIs in France. Despite ICI withdrawal and immunotherapy, 4/6 patients died, and the remaining 2 showed a moderate to severe disability. We show a clear association between ICI use and increased diagnosis of Ma2-PNS. Physicians need to be aware that ICIs can trigger Ma2-PNS because clinical presentation can be challenging.
Identifiants
pubmed: 31454760
pii: 6/6/e604
doi: 10.1212/NXI.0000000000000604
pmc: PMC6705619
pii:
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Antigens, Neoplasm
0
Antineoplastic Agents, Immunological
0
Immunologic Factors
0
Ipilimumab
0
Ma2 antigen
0
Nerve Tissue Proteins
0
Nivolumab
31YO63LBSN
pembrolizumab
DPT0O3T46P
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
Références
N Engl J Med. 1999 Jun 10;340(23):1788-95
pubmed: 10362822
Brain. 2001 Jun;124(Pt 6):1138-48
pubmed: 11353730
Ann Neurol. 2001 Sep;50(3):339-48
pubmed: 11558790
Brain. 2004 Aug;127(Pt 8):1831-44
pubmed: 15215214
J Neurol Neurosurg Psychiatry. 2004 Aug;75(8):1135-40
pubmed: 15258215
Orphanet J Rare Dis. 2007 May 04;2:22
pubmed: 17480225
J Neurol Neurosurg Psychiatry. 2008 Jul;79(7):767-73
pubmed: 18223018
Arch Neurol. 2011 Apr;68(4):521-4
pubmed: 21482933
JAMA Neurol. 2013 Oct;70(10):1305-10
pubmed: 23939463
Endocrinol Metab Clin North Am. 2013 Sep;42(3):453-76
pubmed: 24011880
J Neurol Sci. 2015 Mar 15;350(1-2):105-6
pubmed: 25661887
Lancet Neurol. 2016 Apr;15(4):391-404
pubmed: 26906964
Handb Clin Neurol. 2016;133:147-63
pubmed: 27112676
JAMA Neurol. 2016 Aug 1;73(8):928-33
pubmed: 27271951
Brain. 2016 Nov 1;139(11):2923-2934
pubmed: 27604307
Curr Opin Neurol. 2016 Dec;29(6):806-812
pubmed: 27653290
Oncologist. 2017 Jun;22(6):709-718
pubmed: 28495807
JAMA Neurol. 2017 Oct 1;74(10):1216-1222
pubmed: 28873125
Ann Oncol. 2017 Jul 1;28(suppl_4):iv119-iv142
pubmed: 28881921
Curr Opin Neurol. 2017 Dec;30(6):659-668
pubmed: 28938341
JAMA Oncol. 2018 Feb 1;4(2):173-182
pubmed: 28973656
Nat Rev Neurol. 2017 Dec;13(12):755-763
pubmed: 29104289
Acta Neuropathol. 2018 Apr;135(4):569-579
pubmed: 29299667
Science. 2018 Mar 23;359(6382):1350-1355
pubmed: 29567705
Ann Rheum Dis. 2019 Jan;78(1):150-152
pubmed: 30185415
J Med Case Rep. 2018 Sep 15;12(1):262
pubmed: 30217214
Ther Adv Neurol Disord. 2018 Sep 14;11:1756286418799864
pubmed: 30245744
J Natl Compr Canc Netw. 2018 Oct;16(10):1259-1268
pubmed: 30323094
Neurol Neuroimmunol Neuroinflamm. 2018 Jan 11;5(2):e439
pubmed: 30465016
J Neurol. 2019 Feb;266(2):398-410
pubmed: 30498914
Nat Rev Clin Oncol. 2019 Sep;16(9):535-548
pubmed: 30867573