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Treatment of Myositis Associated With Immune Checkpoint Inhibitors

  • Other CTD: Inflammatory Myopathies (K Saag, Section Editor)
  • Published:
Current Treatment Options in Rheumatology Aims and scope Submit manuscript

Abstract

Purpose of review

To analyze and provide an update of the current therapeutic strategies on immune checkpoint inhibitor-related myositis, including forms with concurrent myocarditis and/or myasthenia. Moreover, we aim to assess the risk of rechallenging with ICI as well as the potential abrogation of antitumor immunity with the immunosuppressive therapy.

Recent findings

Therapeutic recommendations indicate that the best initial approach in patients with myositis is withholding ICI therapy and initiating treatment with corticosteroids. In severe forms, the use of intravenous immunoglobulins, plasma exchange, or additional oral immunosuppressants should be considered. The benefit of new biological drugs has recently been pointed out, highlighting IL-6 receptor inhibitors and Janus kinase inhibitors.

Summary

Corticosteroids are considered as the first-line therapy for patients with myositis. Intensive or rescue therapies may be useful in corticosteroid-refractory patients as well as in those with myasthenia or myocarditis. Prospective studies are needed to better understand the mechanism of myositis so that new targeted therapies could arise. Further research is key to improve the therapeutic options that lead to resolution of ICI-related adverse events while preserving antitumor effects.

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References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. •• Reynolds KL, Guidon AC. Diagnosis and management of immune checkpoint inhibitor-associated neurologic toxicity: illustrative case and review of the literature. Oncologist. 2019;24(4):435–443. Comprehensive recommendations for specific organ system–based toxicity diagnosis and management.

  2. •• Jordan B, Benesova K, Hassel JC, Wick W, Jordan K. How we identify and treat neuromuscular toxicity induced by immune checkpoint inhibitors. ESMO Open. 2021;6(6):100317. A practical review of the therapeutic management algorithm according to severity of neuromuscular irAE following ESMO guidelines.

  3. •• Matas-Garcia A, Milisenda JC, Selva-O’Callaghan A, et al. Emerging PD-1 and PD-1L inhibitors-associated myopathy with a characteristic histopathological pattern. Autoimmun Rev. 2020;19:102455. A characteristic clinical and pathological picture was depicted in the analysis of patients with checkpoint inhibitor-associated myopathy.

  4. Cappelli LC, Bingham CO 3rd. Expert perspective: immune checkpoint inhibitors and rheumatologic complications. Arthritis Rheumatol. 2021;73(4):553–65.

    Article  PubMed  PubMed Central  Google Scholar 

  5. • Kostine M, Finckh A, Bingham CO, Visser K, Leipe J, Schulze-Koops H, et al. EULAR points to consider for the diagnosis and management of rheumatic immune-related adverse events due to cancer immunotherapy with checkpoint inhibitors. Ann Rheum Dis. 2021;80(1):36–48. https://doi.org/10.1136/annrheumdis-2020-217139. A useful guide on the treatment of irM from a rheumatological approach.

  6. •• Weill A, Delyon J, Descamps V, Deschamps L, Dinulescu M, Dupuy A, et al. Treatment strategies and safety of rechallenge in the setting of immune checkpoint inhibitors-related myositis: a national multicentre study. Rheumatology (Oxford). 2021;60(12):5753–5764. A nationwide retrospective study including irM without myocarditis which places special emphasis on the recognition of prognostic factors and the outcome after rechallenging with ICI.

  7. •• Reid P, Cappelli LC. Treatment of rheumatic adverse events of cancer immunotherapy. Best Prast Res Clin Bheuratel. 2022;36(4):101805. https://doi.org/10.1016/jberh.2022.101805. Recommendations based not only on the clinical presentation and severity but also on the goals of treatment.

  8. Alexanderson H, Boström C. Exercise therapy in patients with idiopathic inflammatory myopathies and systemic lupus erythematosus - a systematic literature review. Best Pract Res Clin Rheumatol. 2020;34(2): 101547.

    Article  PubMed  Google Scholar 

  9. Gil-Vila A, Ravichandran N, Selva-O’Callaghan A, et al. COVID-19 vaccination in autoimmune diseases (COVAD) study: vaccine safety in idiopathic inflammatory myopathies. Muscle Nerve. 2022;66(4):426–437.

  10. Steven NM, Fisher BA. Management of rheumatic complications of immune checkpoint inhibitor therapy - an oncological perspective. Rheumatology (Oxford). 2019;58(Suppl 7):vii29-vii39.

  11. Pathak R, Katel A, Massarelli E, Villaflor VM, Sun V, Salgia R. Immune checkpoint inhibitor-induced myocarditis with myositis/myasthenia gravis overlap syndrome: a systematic review of cases. Oncologist. 2021;26(12):1052–61.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Vogrig A, Muñiz-Castrillo S, Farina A, Honnorat J, Joubert B. How to diagnose and manage neurological toxicities of immune checkpoint inhibitors: an update. J Neurol. 2022;269(3):1701–14.

    Article  PubMed  Google Scholar 

  13. Manousakis G. Inflammatory myopathies. Continuum (Minneap Minn). 2022;28(6):1643–62.

    PubMed  Google Scholar 

  14. Suarez-Almazor ME, Pundole X, Abdel-Wahab N, Johnson DB, Gupta D, Glezerman I, et al. Multinational Association of Supportive Care in Cancer (MASCC) 2020 clinical practice recommendations for the management of immune-mediated cardiovascular, rheumatic, and renal toxicities from checkpoint inhibitors. Support Care Cancer. 2020;28(12):6159–73.

    Article  PubMed  Google Scholar 

  15. Cautela J, Zeriouh S, Gaubert M, Bonello L, Laine M, Peyrol M, et al. Intensified immunosuppressive therapy in patients with immune checkpoint inhibitor-induced myocarditis. J Immunother Cancer. 2020;8(2): e001887.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Cuzzubbo S, Carpentier AF. Neurological adverse events of immune checkpoint blockade: from pathophysiology to treatment. Curr Opin Neurol. 2022;35(6):814–22.

    Article  CAS  PubMed  Google Scholar 

  17. Selva-O’Callaghan A, Trallero-Araguás E, Ros J, Gil-Vila A, Lostes J, Agustí A, et al. Management of cancer-associated myositis. Curr Treatm Opt Rheumatol. 2022;8(4):91–104.

  18. Jespersen MS, Fanø S, Stenør C, Møller AK. A case report of immune checkpoint inhibitor-related steroid-refractory myocarditis and myasthenia gravis-like myositis treated with abatacept and mycophenolate mofetil. Eur Heart J Case Rep. 2021;5(11):ytab342.

  19. Bruera S, Suarez-Almazor ME. The effects of glucocorticoids and immunosuppressants on cancer outcomes in checkpoint inhibitor therapy. Front Oncol. 2022;12: 928390.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Punekar SR, Castillo R, Sandigursky S, Cho DC. Role of IVIG in the treatment of autoimmune conditions with concurrent immune checkpoint inhibitors for metastatic cancer. J Immunother. 2021;44(8):335–7.

    Article  CAS  PubMed  Google Scholar 

  21. Jain V, Remley W, Bunag C, Elfasi A, Chuquilin M. Rituximab in refractory myositis and acute neuropathy secondary to checkpoint inhibitor therapy. Cureus. 2022;14(5): e25129.

    PubMed  PubMed Central  Google Scholar 

  22. Liu X, Wu W, Fang L, Liu Y, Chen W. TNF-α inhibitors and other biologic agents for the treatment of immune checkpoint inhibitor-induced myocarditis. Front Immunol. 2022;13: 922782.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Stroud CR, Hegde A, Cherry C, Naqash AR, Sharma N, Addepalli S, et al. Tocilizumab for the management of immune mediated adverse events secondary to PD-1 blockade. J Oncol Pharm Pract. 2019;25(3):551–7.

    Article  CAS  PubMed  Google Scholar 

  24. •• Pinal-Fernandez I, Quintana A, Milisenda JC, Casal-Dominguez M, Muñoz-Braceras S, Derfoul A, et al. Transcriptomic profiling reveals distinct subsets of immune checkpoint inhibitor-induced myositis. Ann Rheum Dis. 2023;82(6):829-836. https://doi.org/10.1136/ard-2022-223792. This article provides novel information about the major overexpressed inflammatory pathways in patients.

  25. Campochiaro C, Farina N, Tomelleri A, Ferrara R, Lazzari C, De Luca G, et al. Tocilizumab for the treatment of immune-related adverse events: a systematic literature review and a multicentre case series. Eur J Intern Med. 2021;93:87–94.

    Article  CAS  PubMed  Google Scholar 

  26. Dimitriou F, Hogan S, Menzies AM, Dummer R, Long GV. Interleukin-6 blockade for prophylaxis and management of immune-related adverse events in cancer immunotherapy. Eur J Cancer. 2021;157:214–24.

    Article  CAS  PubMed  Google Scholar 

  27. Picca A, Valyraki N, Birzu C, Kramkimel N, Hermine O, Zahr N, et al. Anti-interleukin-6 and Janus kinase inhibitors for severe neurologic toxicity of checkpoint inhibitors. Neurol Neuroimmunol Neuroinflamm. 2021;8(6): e1073.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Salem JE, Allenbach Y, Vozy A, Brechot N, Johnson DB, Moslehi JJ, et al. Abatacept for severe immune checkpoint inhibitor-associated myocarditis. N Engl J Med. 2019;380(24):2377–9.

    Article  PubMed  Google Scholar 

  29. Doms J, Prior JO, Peters S, Obeid M. Tocilizumab for refractory severe immune checkpoint inhibitor-associated myocarditis. Ann Oncol. 2020;31(9):1273–5.

    Article  CAS  PubMed  Google Scholar 

  30. Esfahani K, Buhlaiga N, Thébault P, Lapointe R, Johnson NA, Miller WH Jr. Alemtuzumab for immune-related myocarditis due to PD-1 therapy. N Engl J Med. 2019;380(24):2375–6.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Muscle Research Unit, Department of Internal Medicine Service, Hospital Clínic de Barcelona (HCB), Universidad de Barcelona and Center for Biomedical Research On Rare Diseases (CIBERER), C/Villarroel, 170, 08036, Barcelona, Spain

    Ana Matas-García MD & José César Milisenda MD–PhD

  2. Department of Neurology, Hospital Clínic, University of Barcelona, Barcelona, Spain

    Eugenia Martinez-Hernandez MD–PhD

Authors
  1. Ana Matas-García MD
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  2. Eugenia Martinez-Hernandez MD–PhD
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  3. José César Milisenda MD–PhD
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Correspondence to José César Milisenda MD–PhD.

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Conflict of Interest

Ana Matas-García declares no competing interests. Eugenia Martinez-Hernandez declares no competing interests. José César Milisenda declares no competing interests.

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Matas-García, A., Martinez-Hernandez, E. & Milisenda, J.C. Treatment of Myositis Associated With Immune Checkpoint Inhibitors. Curr Treat Options in Rheum 9, 179–191 (2023). https://doi.org/10.1007/s40674-023-00212-0

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