Preprint Article Version 1 This version is not peer-reviewed

Neuromuscular Adverse Events Associated with Anti-PD-1 Monoclonal Antibodies: Systematic Review

Version 1 : Received: 26 September 2018 / Approved: 29 September 2018 / Online: 29 September 2018 (11:28:00 CEST)

A peer-reviewed article of this Preprint also exists.

Johansen, A.; Christensen, S.J.; Scheie, D.; Højgaard, J.L.; Kondziella, D. Neuromuscular adverse events associated with anti-PD-1 monoclonal antibodies: Systematic review. Neurology 2019. Johansen, A.; Christensen, S.J.; Scheie, D.; Højgaard, J.L.; Kondziella, D. Neuromuscular adverse events associated with anti-PD-1 monoclonal antibodies: Systematic review. Neurology 2019.

Journal reference: Neurology 2019
DOI: 10.1212/WNL.0000000000007235

Abstract

Neuromuscular adverse events following cancer treatment with anti-programmed cell death protein 1 (PD-1) monoclonal antibodies are relatively rare, yet potentially fatal. Using the PRISMA approach, we performed a systematic review to characterize the clinical presentation, diagnostic workup, and management of neuromuscular disorders (NMDs) in patients treated with nivolumab or pembrolizumab. Sixty-three publications on 85 patients (mean age 66,9 years (range 34–86); male/female 2.6:1; 59% metastatic melanoma) were identified from selected indexing databases until June 2018. Forty-eight patients had received nivolumab and 39 pembrolizumab. The mean number of PD-1 inhibitor treatment cycles prior to onset of symptoms was 3,6 (range 1–28). Symptoms included oculomotor (47%); respiratory (43%), bulbar (35%), and proximal weakness (35%); as well as muscle pain (28%). Diagnoses were categorized as myasthenia gravis (27%), neuropathy (23%), myopathy (34%) and a combination of these (16%). After critical review of the data, however, evidence did not support the stated NMD diagnosis in 13% of cases, while up to 14% of patients had signs of additional NMDs. PD-1 inhibitor associated myasthenia was associated with cardiac complications in almost 30% of patients and with a more rapid clinical progression compared with idiopathic myasthenia. Mortality was high despite adequate treatment strategies including corticosteroid, IV immunoglobulins and plasmapheresis. In conclusion, clinical presentation of NMDs associated with PD-1 inhibitors is often atypical, with significant overlap between myasthenia gravis and myopathy; and cardiac/respiratory complications are common, leading to more severe disease courses than idiopathic myasthenia.

Subject Areas

adverse events; immune checkpoint inhibitor; myasthenia gravis; myopathy; neuropathy; nivolumab; pembrolizumab

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