Skip to main content

Advertisement

Log in

Immune Checkpoint Inhibitor-Induced Myositis: a Case Report and Literature Review

  • Inflammatory Muscle Disease (I Lundberg, Section Editor)
  • Published:
Current Rheumatology Reports Aims and scope Submit manuscript

Abstract

Purpose of the Review

We clarify clinical characteristics of patients with immune checkpoint inhibitor (ICI)-induced myositis.

Recent Findings

In 13 of 15 cases with ICI-induced myositis, the type of malignancy was melanoma. Eight, 4, and 3 patients received anti-PD-1 alone, anti-CTLA4 alone, and a combination of those, respectively. The mean period to the onset of ICI-induced myositis from the initiation of ICI was 4 weeks. Myocarditis was a complication in five patients. Seven of the patients died. The causes of death were myocarditis in three patients, respiratory muscle paralysis in two patients, and cancer progression in two patients. In patients without myocarditis or respiratory muscle paralysis, the prognosis for myositis was favorable with normalization of the CK levels occurring upon the cessation of ICI and the administration of immunosuppressive agents.

Summary

Myocarditis and respiratory muscle paralysis are the major causes of death as immune-related adverse events in patients with ICI-induced myositis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

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

  1. Chen Z, Hu W, Wang Y, Guo Z, Sun L, Kuwana M. Distinct profiles of myositis-specific autoantibodies in Chinese and Japanese patients with polymyositis/dermatomyositis. Clin Rheumatol. 2015;34(9):1627–31. https://doi.org/10.1007/s10067-015-2935-9.

    Article  PubMed  Google Scholar 

  2. Hill CL, Zhang Y, Sigurgeirsson B, Pukkala E, Mellemkjaer L, Airio A, et al. Frequency of specific cancer types in dermatomyositis and polymyositis: a population-based study. Lancet. 2001;357(9250):96–100. https://doi.org/10.1016/S0140-6736(00)03540-6.

    Article  CAS  PubMed  Google Scholar 

  3. Dankó K, Ponyi A, Molnar AP, András C, Constantin T. Paraneoplastic myopathy. Curr Opin Rheumatol. 2009;21(6):594–8. https://doi.org/10.1097/BOR.0b013e3283317fa5.

    Article  PubMed  Google Scholar 

  4. Franklin C, Livingstone E, Roesch A, Schilling B, Schadendorf D. Immunotherapy in melanoma: recent advances and future directions. Eur J Surg Oncol. 2017;43(3):604–11. https://doi.org/10.1016/j.ejso.2016.07.145.

    Article  CAS  PubMed  Google Scholar 

  5. Kim BJ, Kim JH, Kim HS. Survival benefit of immune checkpoint inhibitors according to the histology in non-small-cell lung cancer: a meta-analysis and review. Oncotarget. 2017;8(31):51779–85. https://doi.org/10.18632/oncotarget.17213.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Byun DJ, Wolchok JD, Rosenberg LM, Girotra M. Cancer immunotherapy - immune checkpoint blockade and associated endocrinopathies. Nat Rev Endocrinol. 2017;13(4):195–207. https://doi.org/10.1038/nrendo.2016.205.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Nishino M, Sholl LM, Hodi FS, Hatabu H, Ramaiya NH. Anti-PD-1-related pneumonitis during cancer immunotherapy. N Engl J Med. 2015;373(3):288–90. https://doi.org/10.1056/NEJMc1505197.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Danlos FX, Voisin AL, Dyevre V, Michot JM, Routier E, Taillade L, et al. Safety and efficacy of anti-programmed death 1 antibodies in patients with cancer and pre-existing autoimmune or inflammatory disease. Eur J Cancer. 2018;91:21–9. https://doi.org/10.1016/j.ejca.2017.12.008.

    Article  CAS  PubMed  Google Scholar 

  9. • Johnson DB, Sullivan RJ, Ott PA, Carlino MS, Khushalani NI, Ye F, et al. Ipilimumab therapy in patients with advanced melanoma and preexisting autoimmune disorders. JAMA Oncol. 2016;2(2):234–40. https://doi.org/10.1001/jamaoncol.2015.4368. This study demonstrated that safety and efficacy of ipilimumab therapy in patients with advanced melanoma with preexisting autoimmune disorders. Ipilimumab therapy is associated with exacerbations of autoimmune disease.

    Article  PubMed  Google Scholar 

  10. • Menzies AM, Johnson DB, Ramanujam S, Atkinson VG, ANM W, Park JJ, et al. Anti-PD-1 therapy in patients with advanced melanoma and preexisting autoimmune disorders or major toxicity with ipilimumab. Ann Oncol. 2017;28(2):368–76. https://doi.org/10.1093/annonc/mdw443. This study supported that anti-PD-1 can be administered safely and can achieve clinical benefit in patients with preexisting autoimmune disorders.

    Article  CAS  PubMed  Google Scholar 

  11. • Belkhir R, Burel SL, Dunogeant L, Marabelle A, Hollebecque A, Besse B, et al. Rheumatoid arthritis and polymyalgia rheumatica occurring after immune checkpoint inhibitor treatment. Ann Rheum Dis. 2017;76(10):1747–50. https://doi.org/10.1136/annrheumdis-2017-211216. This study showed that all cases with rheumatoid arthritis occurring after immune checkpoint inhibitor therapy responded to corticosteroids or with immunosuppressive therapy.

    Article  CAS  PubMed  Google Scholar 

  12. •• Johnson DB, Balko JM, Compton ML, Chalkias S, Gorham J, Xu Y, et al. Fulminant myocarditis with combination immune checkpoint blockade. N Engl J Med. 2016;375(18):1749–55. https://doi.org/10.1056/NEJMoa1609214. This study demonstrated the pathophysiology of immune checkpoint inhibitor-induced myositis. Selective clonal T cell populations infiltrating the myocardium were identical to those present in tumors and skeletal muscle.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Forman MS, Nakamura M, Mimori T, Gelpi C, Hardin JA. Detection of antibodies to small nuclear ribonucleoproteins and small cytoplasmic ribonucleoproteins using unlabeled cell extracts. Arthritis Rheum. 1985;28(12):1356–61. https://doi.org/10.1002/art.1780281207.

    Article  CAS  PubMed  Google Scholar 

  14. Nakashima R, Imura Y, Hosono Y, Seto M, Murakami A, Watanabe K, et al. The multicenter study of a new assay for simultaneous detection of multiple anti-aminoacyl-tRNA synthetases in myositis and interstitial pneumonia. PLoS One. 2014;9(1):e85062. https://doi.org/10.1371/journal.pone.0085062.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Vallet H, Gaillet A, Weiss N, Vanhaecke C, Saheb S, Touitou V, et al. Pembrolizumab-induced necrotic myositis in a patient with metastatic melanoma. Ann Oncol. 2016;27(7):1352–3. https://doi.org/10.1093/annonc/mdw126.

    Article  CAS  PubMed  Google Scholar 

  16. Haddox CL, Shenoy N, Shah KK, Kao JC, Jain S, Halfdanarson TR, et al. Pembrolizumab induced bulbar myopathy and respiratory failure with necrotizing myositis of the diaphragm. Ann Oncol. 2017;28(3):673–5. https://doi.org/10.1093/annonc/mdw655.

    Article  CAS  PubMed  Google Scholar 

  17. Diamantopoulos PT, Tsatsou K, Benopoulou O, Anastasopoulou A, Gogas H. Inflammatory myopathy and axonal neuropathy in a patient with melanoma following pembrolizumab treatment. J Immunother. 2017;40(6):221–3. https://doi.org/10.1097/CJI.0000000000000172.

    Article  PubMed  Google Scholar 

  18. Yoshioka M, Kambe N, Yamamoto Y, Suehiro K, Matsue H. Case of respiratory discomfort due to myositis after administration of nivolumab. J Dermatol. 2015;42(10):1008–9. https://doi.org/10.1111/1346-8138.12991.

    Article  PubMed  Google Scholar 

  19. •• Kimura T, Fukushima S, Miyashita A, Aoi J, Jinnin M, Kosaka T, et al. Myasthenic crisis and polymyositis induced by one dose of nivolumab. Cancer Sci. 2016;107(7):1055–8. https://doi.org/10.1111/cas.12961. This research showed T cell receptor repertoire analysis using next-generation sequencing technologies and identified infiltration of clonally expanded T cell populations in the skeletal muscle after nivolumab treatment. Nivolumab treatment drastically decreased CD4 and FoxP3 expression levels in peripheral blood.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Fox E, Dabrow M, Ochsner G. A case of nivolumab-induced myositis. Oncologist. 2016;21(12):e3. https://doi.org/10.1634/theoncologist.2016-0170.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Behling J, Kaes J, Münzel T, Grabbe S, Loquai C. New-onset third-degree atrioventricular block because of autoimmune-induced myositis under treatment with anti-programmed cell death-1 (nivolumab) for metastatic melanoma. Melanoma Res. 2017;27(2):155–8. https://doi.org/10.1097/CMR.0000000000000314.

    Article  CAS  PubMed  Google Scholar 

  22. Hunter G, Voll C, Robinson CA. Autoimmune inflammatory myopathy after treatment with ipilimumab. Can J Neurol Sci. 2009;36(4):518–20. https://doi.org/10.1017/S0317167100007939.

    Article  PubMed  Google Scholar 

  23. Sheik Ali S, Goddard AL, Luke JJ, Donahue H, Todd DJ, Werchniak A, et al. Drug-associated dermatomyositis following ipilimumab therapy: a novel immune-mediated adverse event associated with cytotoxic T-lymphocyte antigen 4 blockade. JAMA Dermatol. 2015;151(2):195–9. https://doi.org/10.1001/jamadermatol.2014.2233.

    Article  PubMed  Google Scholar 

  24. Liao B, Shroff S, Kamiya-Matsuoka C, Tummala S. Atypical neurological complications of ipilimumab therapy in patients with metastatic melanoma. Neuro-Oncology. 2014;16(4):589–93. https://doi.org/10.1093/neuonc/nou001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Yamaguchi Y, Abe R, Haga N, Shimizu H. A case of drug-associated dermatomyositis following ipilimumab therapy. Eur J Dermatol 2016;26(3):320–321. https://doi.org/10.1684/ejd.2016.2770.

  26. Bilen MA, Subudhi SK, Gao J, Tannir NM, Tu SM, Sharma P. Acute rhabdomyolysis with severe polymyositis following ipilimumab-nivolumab treatment in a cancer patient with elevated anti-striated muscle antibody. J Immunother Cancer. 2016;4(36):36. https://doi.org/10.1186/s40425-016-0139-8.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Fischer A, Antoniou KM, Brown KK, Cadranel J, Corte TJ, du Bois RM, et al. An official European Respiratory Society/American Thoracic Society research statement: interstitial pneumonia with autoimmune features. Eur Respir J. 2015;46(4):976–87. https://doi.org/10.1183/13993003.00150-2015.

    Article  CAS  Google Scholar 

  28. Fujimoto M, Hamaguchi Y, Kaji K, Matsushita T, Ichimura Y, Kodera M, et al. Myositis-specific anti-155/140 autoantibodies target transcription intermediary factor 1 family proteins. Arthritis Rheum. 2012;64(2):513–22. https://doi.org/10.1002/art.33403.

    Article  CAS  PubMed  Google Scholar 

  29. Dalakas MC. Pathophysiology of inflammatory and autoimmune myopathies. Presse Med. 2011;40(4 Pt 2):e237–47. https://doi.org/10.1016/j.lpm.2011.01.005.

    Article  PubMed  Google Scholar 

  30. Kostine M, Rouxel L, Barnetche T, Veillon R, Martin F, Dutriaux C, et al. Rheumatic disorders associated with immune checkpoint inhibitors in patients with cancer-clinical aspects and relationship with tumour response: a single-centre prospective cohort study. Ann Rheum Dis. 2018;77(3):393–8. https://doi.org/10.1136/annrheumdis-2017-212257.

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This study was supported in part by research grants for intractable diseases of Autoimmune Diseases from the Ministry of Health, Labour and Welfare, Japan.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Takahisa Gono.

Ethics declarations

Conflict of Interest

The authors declare no conflicts of interest in this work. Outside the submitted work, Kadota H, Shirai Y, and Okazaki Y have nothing to disclose. Gono T, Takeno M, and Kuwana M have relevant financial activities outside the submitted work as follows: Gono T, personal fees from Astellas Pharma, personal fees from Chugai Pharmaceutical, personal fees from Daiichi sankyo, personal fees from Janssen Pharmaceutical, personal fees from Mitsubishi Tanabe Pharma, personal fees from Ono Pharmaceutical; Takeno M, personal fees from Celgene, personal fees from Tanabe-Mitsubishi, Co, personal fees from Eizai, Abbbie, grants from Novortis; Kuwana M, grants and personal fees from Chugai Pharmaceutical, grants and personal fees from Mitsubishi Tanabe Pharma, grants and personal fees from Ono Pharmaceutical, grants and personal fees from Pfizer, personal fees from Janssen Pharmaceutical, grants and personal fees from Astellas Pharma, grants and personal fees from Esai, personal fees from Boehringer Ingelheim, personal fees from Bayer, personal fees from Corbus, personal fees from Reata.

Ethics Approval and Consent to Participate

This study was approved by the ethics committee of Nippon Medical School Hospital (approval number 28-12-680) and was conducted in accordance with the Declaration of Helsinki. Our patient provided informed consent to participate in this study and consent for the use of the data.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Inflammatory Muscle Disease

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kadota, H., Gono, T., Shirai, Y. et al. Immune Checkpoint Inhibitor-Induced Myositis: a Case Report and Literature Review. Curr Rheumatol Rep 21, 10 (2019). https://doi.org/10.1007/s11926-019-0811-3

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11926-019-0811-3

Keywords

Navigation