Immune checkpoint inhibitor related myasthenia gravis: single center experience and systematic review of the literature.
Immune checkpoint inhibitors
Immunotherapy
Ipilimumab
Myasthenia gravis
Nivolumab
Pembrolizumab
Journal
Journal for immunotherapy of cancer
ISSN: 2051-1426
Titre abrégé: J Immunother Cancer
Pays: England
ID NLM: 101620585
Informations de publication
Date de publication:
21 11 2019
21 11 2019
Historique:
received:
14
08
2019
accepted:
05
10
2019
entrez:
23
11
2019
pubmed:
23
11
2019
medline:
22
7
2020
Statut:
epublish
Résumé
Myasthenia gravis (MG) is a rare but life-threatening adverse event of immune checkpoint inhibitors (ICI). Given the limited evidence, data from a large cohort of patients is needed to aid in recognition and management of this fatal complication. We reviewed our institutional databases to identify patients who had cancer and MG in the setting of ICI. We systematically reviewed the literature through August 2018 to identify all similar reported patients. We collected data on clinical and diagnostic features, management, and outcomes of these cases. Sixty-five patients were identified. Median age was 73 years; 42 (65%) were males, 31 (48%) had metastatic melanoma, and 13 (20%) had a preexisting MG before ICI initiation. Most patients received anti-PD-1 (82%). Sixty-three patients (97%) developed ICI-related MG (new onset or disease flare) after a median of 4 weeks (1 to 16 weeks) of ICI initiation. Twenty-four patients (37%) experienced concurrent myositis, and respiratory failure occurred in 29 (45%). ICI was discontinued in 61 patients (97%). Death was reported in 24 patients (38%); 15 (23%) due to MG complication. A better outcome was observed in patients who received intravenous immunoglobulin (IVIG) or plasmapheresis (PLEX) as first-line therapy than in those who received steroids alone (95% vs 63% improvement of MG symptoms, p = 0.011). MG is a life-threatening adverse event of acute onset and rapid progression after ICI initiation. Early use of IVIG or PLEX, regardless of initial symptoms severity, may lead to better outcomes than steroids alone. Our data suggest the need to reassess the current recommendations for management of ICI-related MG until prospective longitudinal studies are conducted to establish the ideal management approach for these patients.
Sections du résumé
BACKGROUND
Myasthenia gravis (MG) is a rare but life-threatening adverse event of immune checkpoint inhibitors (ICI). Given the limited evidence, data from a large cohort of patients is needed to aid in recognition and management of this fatal complication.
METHODS
We reviewed our institutional databases to identify patients who had cancer and MG in the setting of ICI. We systematically reviewed the literature through August 2018 to identify all similar reported patients. We collected data on clinical and diagnostic features, management, and outcomes of these cases.
RESULTS
Sixty-five patients were identified. Median age was 73 years; 42 (65%) were males, 31 (48%) had metastatic melanoma, and 13 (20%) had a preexisting MG before ICI initiation. Most patients received anti-PD-1 (82%). Sixty-three patients (97%) developed ICI-related MG (new onset or disease flare) after a median of 4 weeks (1 to 16 weeks) of ICI initiation. Twenty-four patients (37%) experienced concurrent myositis, and respiratory failure occurred in 29 (45%). ICI was discontinued in 61 patients (97%). Death was reported in 24 patients (38%); 15 (23%) due to MG complication. A better outcome was observed in patients who received intravenous immunoglobulin (IVIG) or plasmapheresis (PLEX) as first-line therapy than in those who received steroids alone (95% vs 63% improvement of MG symptoms, p = 0.011).
CONCLUSIONS
MG is a life-threatening adverse event of acute onset and rapid progression after ICI initiation. Early use of IVIG or PLEX, regardless of initial symptoms severity, may lead to better outcomes than steroids alone. Our data suggest the need to reassess the current recommendations for management of ICI-related MG until prospective longitudinal studies are conducted to establish the ideal management approach for these patients.
Identifiants
pubmed: 31753014
doi: 10.1186/s40425-019-0774-y
pii: 10.1186/s40425-019-0774-y
pmc: PMC6868691
doi:
Substances chimiques
Antineoplastic Agents, Immunological
0
Biomarkers
0
Types de publication
Journal Article
Meta-Analysis
Research Support, N.I.H., Extramural
Review
Systematic Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
319Subventions
Organisme : NCI NIH HHS
ID : P30 CA016672
Pays : United States
Références
Medicine (Baltimore). 2017 Jul;96(27):e7350
pubmed: 28682883
Semin Arthritis Rheum. 2019 Feb;48(4):736-740
pubmed: 29909921
N Engl J Med. 2017 Nov 16;377(20):1919-1929
pubmed: 28885881
Cancer Sci. 2016 Jul;107(7):1055-8
pubmed: 27420474
Clin Pharmacokinet. 2019 Jul;58(7):835-857
pubmed: 30815848
Acta Neurol Scand. 1984 Sep;70(3):176-84
pubmed: 6507031
J Immunother Cancer. 2019 May 22;7(1):134
pubmed: 31118078
Curr Opin Neurol. 1998 Jun;11(3):233-4
pubmed: 9642541
J Neurol. 1990 Oct;237(6):339-44
pubmed: 2277266
Muscle Nerve. 2014 Jan;49(1):30-4
pubmed: 23625360
Eur J Cancer. 2017 Mar;73:1-8
pubmed: 28064139
Neurotherapeutics. 2016 Jan;13(1):118-31
pubmed: 26510558
Semin Arthritis Rheum. 2019 Feb;48(4):745-751
pubmed: 29958689
J Clin Oncol. 2018 Jun 10;36(17):1714-1768
pubmed: 29442540
Oncologist. 2017 Jun;22(6):709-718
pubmed: 28495807
Case Rep Oncol. 2017 Sep 6;10(3):809-812
pubmed: 29070994
Lancet Oncol. 2015 May;16(5):522-30
pubmed: 25840693
Muscle Nerve. 2018 Jan 17;:null
pubmed: 29342325
N Engl J Med. 2017 Nov 9;377(19):1824-1835
pubmed: 28891423
Muscle Nerve. 2019 Dec;60(6):693-699
pubmed: 31469909
J Neurol. 2016 Aug;263(8):1473-94
pubmed: 26886206
Ann Oncol. 2017 Feb 1;28(2):368-376
pubmed: 27687304
J Natl Compr Canc Netw. 2019 Mar 1;17(3):255-289
pubmed: 30865922
Expert Opin Drug Metab Toxicol. 2016 Oct;12(10):1247-53
pubmed: 27485741
Neuroepidemiology. 2015;44(4):221-31
pubmed: 26068011
Neuromuscul Disord. 2017 Mar;27(3):266-268
pubmed: 28109638
Ther Adv Neurol Disord. 2018 Sep 14;11:1756286418799864
pubmed: 30245744
Eur J Cancer. 2017 Sep;82:128-136
pubmed: 28666240
Muscle Nerve. 2008 Feb;37(2):141-9
pubmed: 18059039
Ann Intern Med. 2018 Jan 16;168(2):121-130
pubmed: 29297009
N Engl J Med. 2018 May 10;378(19):1789-1801
pubmed: 29658430
Arch Neurol. 2009 Nov;66(11):1334-8
pubmed: 19752287
Pharmacoepidemiol Drug Saf. 2007 May;16(5):581-7
pubmed: 17471601
Melanoma Res. 2017 Apr;27(2):152-154
pubmed: 27776019
Curr Neurol Neurosci Rep. 2018 Aug 4;18(10):63
pubmed: 30078154
Neurology. 1986 May;36(5):729-32
pubmed: 3703276
Neurology. 2011 Jun 7;76(23):2017-23
pubmed: 21562253
J Clin Neurosci. 2006 Dec;13(10):1006-10
pubmed: 17074487
Acta Neurol Scand. 2014 Oct;130(4):211-21
pubmed: 25069701
Eur J Cancer. 2016 Dec;69:39-42
pubmed: 27816830
Neurology. 2007 Mar 13;68(11):837-41
pubmed: 17353471
Arch Neurol. 2005 Mar;62(3):442-6
pubmed: 15767509
Ann Neurol. 1997 Jun;41(6):789-96
pubmed: 9189040
Neurology. 2017 Sep 12;89(11):1127-1134
pubmed: 28821685
Jpn J Clin Oncol. 2016 Jan;46(1):86-8
pubmed: 26491202