PD-1 Inhibitor-associated Myopathies: Emerging Immune-mediated Myopathies

Teerin Liewluck, Justin C. Kao, Michelle M Mauermann

Research output: Contribution to journalArticle

59 Scopus citations

Abstract

Programmed death-1 (PD-1) inhibitors are increasingly used in cancer immunotherapy. Various immune-related adverse events are reported, including infrequent individual case reports of myositis or rhabdomyolysis. The frequency and diagnostic spectrum of immune-related adverse events affecting skeletal muscle in PD-1 inhibitor-treated patients are unknown. We searched the Mayo Clinic Pharmacy database (2014-2016) to identify patients who developed myopathies during or after PD-1 inhibitor therapy. Among 654 cancer patients received PD-1 inhibitors (pembrolizumab=389; nivolumab=264; both=1), we identified 5 patients (pembrolizumab=5) with biopsy-proven myopathies (2 necrotizing myopathy, 1 early dermatomyositis, and 2 nonspecific myopathy). Four patients developed concomitant autoimmune disorders. Weakness occurred after a median of 2 treatments (range, 1-4). All patients had proximal or axial weakness. Four patients had either bulbar or extraocular weakness, but only 1 patient had acetylcholine receptor antibodies. Creatine kinase levels were elevated in 3 patients (necrotizing myopathy=2; nonspecific myopathy=1). Brain magnetic resonance imaging revealed abnormal T2 signal and enhancement of extraocular muscles in 1 patient with ophthalmoparesis. Pembrolizumab was discontinued in all patients. All patients received immunosuppressive therapy, with fatal outcome in 2 necrotizing myopathy patients and favorable outcome in others. We conclude that myopathy is a rare, but unique complication of PD-1 inhibitors with frequent involvement of extraocular or bulbar muscles, mimicking myasthenia gravis. Muscle biopsy is an important test for PD-1 inhibitor-treated patients who develop oculobulbar weakness and hyperCKemia, to distinguish patients with necrotizing myopathy from myasthenia gravis. Necrotizing myopathy patients may require more aggressive immunotherapy due to their grave prognosis.

Original languageEnglish (US)
Pages (from-to)208-211
Number of pages4
JournalJournal of Immunotherapy
Volume41
Issue number4
DOIs
StatePublished - Jan 1 2018

Keywords

  • Immune checkpoints
  • Myasthenia gravis
  • Myopathy
  • Necrotizing myopathy
  • Nivolumab
  • PD-1 inhibitors
  • Pembrolizumab

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology
  • Cancer Research

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