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Pre-existing antiacetylcholine receptor autoantibodies and B cell lymphopaenia are associated with the development of myositis in patients with thymoma treated with avelumab, an immune checkpoint inhibitor targeting programmed death-ligand 1
  1. Andrew L Mammen1,
  2. Arun Rajan2,
  3. Katherine Pak1,
  4. Tanya Lehky3,
  5. Livia Casciola-Rosen4,
  6. Renee N Donahue5,
  7. Lauren M Lepone5,
  8. Anastasia Zekeridou6,
  9. Sean J Pittock6,
  10. Raffit Hassan2,
  11. Jeffrey Schlom5,
  12. James L Gulley5,7
  1. 1 Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA
  2. 2 Thoracic and Gastrointestinal Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
  3. 3 Electromyography Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA
  4. 4 Division of Rheumatology, Department of Medicine, The Johns Hopkins Hospital, Baltimore, Maryland, USA
  5. 5 Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
  6. 6 Neuroimmunology Laboratory, Mayo Clinic, Rochester, Minnesota, USA
  7. 7 Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
  1. Correspondence to Dr Andrew L Mammen, Muscle Diseases Unit, Laboratory of Muscle Stem Cells and Gene Expression, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA; andrew.mammen{at}nih.gov

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Immune checkpoint inhibitors enhance the immune response against tumours but may also trigger immune-related adverse events (IRAEs). Myositis is a rare IRAE. For example, creatine kinase (CK) elevations occurred in just 0.3% of those treated with avelumab, an antiprogrammed death-ligand 1 antibody.1

Thymomas are the most common anterior mediastinal masses in adults. Since effective systemic therapies for thymic epithelial tumours are lacking, we included seven patients with recurrent thymoma and one patient with recurrent thymic carcinoma in a phase I trial of avelumab (NCT01772004). Details regarding this trial have been published separately.2

Myasthenia gravis and myositis occur in up to 30% and 5% of patients with thymoma, respectively.3 Although no patient had a history of autoimmunity or weakness and each had normal baseline CK levels, four patients developed weakness and elevated CK levels, ranging from 762 IU/L to 16 037 IU/L, within 5 weeks of avelumab administration (see online supplementary text and table 1). CK levels normalised in patients within weeks of stopping avelumab and starting immunosuppressive therapy. Of note, …

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Footnotes

  • ALM and AR contributed equally.

  • Handling editor Josef S Smolen

  • Contributors ALM, AR, RND and JLG designed the study, collected the data, analysed the results and wrote significant portions of the manuscript. TL, AZ, SJP, JS and JLG designed aspects of the study, collected the data and analysed the results. KP, LC-R and LML contributed to clinical data and analysed the results. All authors revised the manuscript critically for important intellectual content and approved the final version.

  • Funding This work was financially supported by the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the National Cancer Institute of the National Institutes of Health. LC-R is funded in part by the Donald B and Dorothy L Stabler Foundation.

  • Competing interests None declared.

  • Patient consent Not required.

  • Ethics approval NIH IRB.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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