Immune checkpoint inhibitors are used in metastatic melanoma with good efficacy and safety profile. We report the first case of an inflammatory demyelinating disease of the central nervous system during treatment with Pembrolizumab and discuss the evidence in the literature supporting its causative role. The patient had a good clinical recovery after intravenous steroids, plasma exchange and discontinuation of Pembrolizumab. Due to the expected increase in the importance of immune checkpoint inhibitors in cancer treatment, it is important to be aware of neurological adverse events, as early treatment usually leads to good clinical responses.
DeeksED.Pembrolizumab: A review in advanced melanoma. Drugs2016; 76(3): 375–386.
2.
Martin-LiberalJKordbachehTLarkinJ.Safety of pembrolizumab for the treatment of melanoma. Expert Opin Drug Saf2015; 14(6): 957–964.
3.
AliAKWatsonDE.Pharmacovigilance assessment of immune-mediated reactions reported for checkpoint inhibitor cancer immunotherapies. Pharmacotherapy2017; 37(11): 1383–1390.
4.
KaoJCLiaoBMarkovicSNet al. Neurological complications associated with anti-programmed death 1 (PD-1) antibodies. JAMA Neurol2017; 74(10): 1216–1222.
TakizawaSKaneyamaTTsuganeSet al. Role of the Programmed Death-1 (PD-1) pathway in regulation of Theiler’s murine encephalomyelitis virus-induced demyelinating disease. J Neuroimmunol2014; 274(1–2): 78–85.
7.
AsgariNNielsenCStenagerEet al. HLA, PTPN22 and PD-1 associations as markers of autoimmunity in neuromyelitis optica. Mult Scler2012; 18(1): 23–30.
8.
KronerAMehlingMHemmerBet al. A PD-1 polymorphism is associated with disease progression in multiple sclerosis. Ann Neurol2005; 58(1): 50–57.
9.
CaoYNylanderARamananSet al. CNS demyelination and enhanced myelin-reactive responses after ipilimumab treatment. Neurology2016; 86(16): 1553–1556.
10.
GerdesLAHeldKBeltránEet al. CTLA4 as immunological checkpoint in the development of multiple sclerosis. Ann Neurol2016; 80(2): 294–300.
11.
GettingsEJHackettCTScottTF.Severe relapse in a multiple sclerosis patient associated with ipilimumab treatment of melanoma. Mult Scler2015; 21(5): 670.
12.
De MaleissyeMFNicolasGSaiagP.Pembrolizumab-induced demyelinating polyradiculoneuropathy. N Engl J Med2016; 375(3): 296–297.
