Risk of immunotherapy-related narcolepsy in genetically predisposed patients: a case report of narcolepsy after administration of pembrolizumab

Abstract

BackgroundImmune-related adverse events associated with immune checkpoint therapy cause autoimmune disease-like symptoms. People who carry specific genotypes or haplotypes of human leucocyte antigen (HLA) are known to be predisposed to develop autoimmune diseases including narcolepsy. Immunotherapy could be a trigger to develop narcolepsy in predisposing HLA positive patients.Case presentationA 66-year-old woman with stage IVB endometrial carcinosarcoma experienced daytime sleepiness and temporary muscle weakness 14 days after the administration of an immune checkpoint inhibitor, pembrolizumab. These were consistent with the main symptoms of narcolepsy with cataplexy. This patient carried a highly predisposing HLA haplotype for narcolepsy; HLA-DQB1*06:02, DRB1*15:01, DQA1*01:02 and DRB5*01:01:01. A hypocretin-1/orexin-A concentration in the patient’s cerebrospinal fluid was low at 9.6 pg/mL in ELISA, and 155.5 pg/mL in radioimmunoassay that was below the normal level of 200 pg/mL. Therefore, she was diagnosed with narcolepsy tentatively according to the International Classification of Sleep Disorders, third edition diagnostic criteria for narcolepsy. The onset of narcolepsy in the 60s is very rare, and narcoleptic symptoms in our patient were likely to be caused by pembrolizumab.ConclusionsThis case suggests that treatment with immune checkpoint inhibitors potentially causes narcolepsy in genetically predisposed patients.

Insomnia in patients treated with checkpoint inhibitors for cancer: A meta-analysis

“…Interestingly, on the other side of the spectrum of sleep disorders, narcolepsy type 1 is thought to have autoimmune aetiology and T cells directed against hypocretin/orexin neurons have been identified in some patients ( 91 ). A case report has been published of narcolepsy possibly caused by pembrolizumab ( 92 ).…”

Clinical analysis and literature review of two paediatric cases of anti-IgLON5 antibody-related encephalitis

“…In allele is also considered a risk factor for NT1 (27), and immunosuppressive treatment can induce narcolepsy in genetically susceptible patients (28). The HLA-DQB*05:02 allele is highly associated with AQP4-positive Neuromyelitis Optica Spectrum Disorder (NMOSD) in the Chinese population (29) and is a high-risk factor for the onset of Myasthenia Gravis (30), particularly in MuSKrelated Myasthenia Gravis (31).…”