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Systemic Vasculitis Associated With Immune Check Point Inhibition: Analysis and Review

  • Vasculitis (L Espinoza, Section Editor)
  • Published:
Current Rheumatology Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Immunotherapy with immune checkpoint inhibitors (ICIs) has become a well-established modality to treat a number of different malignancies, especially in cases with advanced stages and/or recurrent diseases. These agents have been associated with development of a variety of autoimmune disorders as immune-related adverse events (IRAEs or irAEs). This review focuses on development of vasculitis with use of ICI.

Recent Findings

Available information on vasculitis associated with immune checkpoint inhibition is limited primarily to case reports at this time. Most immune-related adverse events will not present as vasculitis, and it is an uncommon manifestation and/or is under-reported. There are no current well-established guidelines for treating vasculitis associated with ICIs; initial management would usually start with consideration of discontinuing the ICI and administering corticosteroids. Collaboration between treating oncologists and rheumatologists is necessary for a combined approach to management.

Summary

While arthralgias, myalgias, and inflammatory arthritis frequently occur as irAEs, vasculitis is an uncommon presentation. Vasculitis has been reported with all of the available ICI agents, and there seems to be no clear difference in the risk based on small numbers. Large vessel vasculitis and vasculitis of the nervous system were the most commonly reported types of vasculitis but cases of vasculitis involving medium and small vessels have also been reported. It is challenging to know if the underlying disease or ICIs are the main culprit in development of vasculitis and requires a collaborative relationship between the treating oncologist and rheumatologist. Except in very mild cases, development of vasculitis during ICI therapy requires temporary or permanent discontinuation of ICI.

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References

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

  1. Sharon E, Streicher H, Goncalves P, Chen HX. Immune checkpoint inhibitors in clinical trials. Chin J Cancer. 2014;33:434–44.

    Article  CAS  Google Scholar 

  2. Rosenberg SA, Yang JC, Restifo NP. Cancer immunotherapy: moving beyond current vaccines. Nat Med. 2004;10:909–15.

    Article  CAS  Google Scholar 

  3. Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012;12:252–64.

    Article  CAS  Google Scholar 

  4. Friedman CF, Proverbs-Singh TA, Postow MA. Treatment of the immune-related adverse effects of immune checkpoint inhibitors: a review. JAMA Oncol. 2016;2:1346–53.

    Article  Google Scholar 

  5. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology. version 2. 2018. https://www.nccn.org/professionals/physician_gls/default.aspx.

  6. • Richter MD, Crowson C, Kottschade LA, Finnes HD, Markovic SN, Thanarajasingam U. Rheumatic syndromes associated with immune-checkpoint inhibitors: a single-center cohort of 61 patients. Arthritis Rheum. 2019;71(3):468–75 Rheumatic immune-related adverse effects from immune checkpoint inhibitors were examined retrospectively in a cohort of 61 patients in an effort to better understand the prevalence, presentation, and management of these patients. Although a small sample size, the study shows that vasculitis was less common compared with other Rh-irAEs.

    Article  CAS  Google Scholar 

  7. •• Daxini A, Cronin K, Sreih AG. Vasculitis associated with immune checkpoint inhibitors- a systematic review. Clin Rheumatol. 2018;37(9):2579–84 This study reviewed the available literature on the cases of vasculitis in the setting of immune checkpoint inhibition. Each case of vasculitis was analyzed by type, presenting features, treatment, and outcome.

    Article  Google Scholar 

  8. Postow MA, Sidlow R, Hellman MD. Immune-related adverse events associated with immune checkpoint blockade. N Engl J Med. 2018;378:158–68.

    Article  CAS  Google Scholar 

  9. Watanabe R, Zhang H, Berry G, Vaglio A, Goronzy JJ, Weyand CM. Immunoinhibitory checkpoint deficiency in medium and large vessel vasculitis. Am J Physiol Heart Circ Physiol. 2017;312(5):H1052–9.

    Article  Google Scholar 

  10. •• Brahmer J, Lacchetti C, Schneider B, et al. Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 36:1714–68 This systematic review looked at the toxicities associated with immune checkpoint inhibition and broke it down by organ system to provide awareness of the adverse effects as well as a clinical practice guideline for management of each type of toxicity.

  11. Goldstein BL, Gedmintas L, Todd DJ. Drug-associated polymyalgia rheumatic/giant cell arteritis occurring in two patients after treatment with ipilimumab, an antagonist of CTLA-4. Arthritis Rheum. 2014;66:768–9.

    Article  Google Scholar 

  12. Pinkston OFB, Wang B. Type and frequency of immune-related adverse reactions in patients treated with pembrolizumab (Keytruda), a monoclonal antibody directed against PD-1, in advanced melanoma at a single institution. [abstract]. Arthritis Rheum. 2016;68(sppl 10).

  13. Abdel Wahab N, Shah M, Suarez-Almazor ME. Adverse events associated with immune checkpoint blockade in patients with cancer: a systematic review of case reports. PLoS One. 2016;11:e0160221.

    Article  Google Scholar 

  14. Roy AK, Tathireddy HR, Roy M. Aftermath of induced inflammation: acute periaortitis due to nivolimumab therapy. BMJ Case Rep:2017.

  15. Cappelli LC, Shah AA, Bingham CO. Immune-related adverse effects of cancer immunotherapy- implications for rheumatology. Rheum Dis Clin N Am. 2017;43:65–78.

    Article  Google Scholar 

  16. Ban BH Crowe J, Graham RM. Rheumatology case report immune-related aortitis associated with ipilimumab. The Rheumatologist 2017.

  17. Minor DR, Bunker SR, Doyle J. Lymphocytic vasculitis of the uterus in a patient with melanoma receiving ipilimumab. J Clin Oncol. 2013;31:e356.

    Article  Google Scholar 

  18. Liao B, Wang W, Hammack J, Mauermann M. Vasculitic neuropathy in the setting of nivolumab therapy for metastatic mesothelioma. Ann Neurol. 2016;80:M279.

    Google Scholar 

  19. Aya F, Ruiz-Esquide V, Vilado M, Font C, Prieto-Gonzalez S, Prat A, et al. Vasculitic neuropathy induced by pembrolizumab. Ann Oncol. 2017;28:433–4.

    CAS  PubMed  Google Scholar 

  20. Arellano K, Mosley JC, Moore DC. Case report of ipilimumab-induced diffuse, nonnecrotizing granulomatous lymphadenitis and granulomatous vasculitis. J Pharm Pract. 2018;31:227–9.

    Article  Google Scholar 

  21. Kao JC, Liao B, Markovic SN, Klein CJ, Naddaf E, Staff NP, et al. Neurological complications associated with anti-programmed death 1 (PD-1) antibodies. JAMA Neurol. 2017;74:1216–22.

    Article  Google Scholar 

  22. Padda A, Schiopu E, Sovich J, Ma V, Alva A, Fecher L. Ipilimumab induced digital vasculitis. J immunother Cancer. 2018;6(1):12.

    Article  Google Scholar 

  23. Comont T, Sibaud V, Mourey L, Cougoul P, Beyne-Rauzy O. Immune checkpoint inhibitor-related acral vasculitis. J Immunother Cancer. 2018;6(1):120.

    Article  Google Scholar 

  24. Le Burel S, Champiat S, Routier E, Aspeslagh S, Albiges L, Szwebel T-A, et al. Onset of connective tissue disease following anti-PD1/PD-L1 cancer immunotherapy. Ann Rheum Dis. 2018;77:468–70.

    Article  Google Scholar 

  25. Gambichler T, Strutzmann S, Tannapfel A, Susok L. Paraneoplastic acral vascular syndrome in a patient with metastatic melanoma under immune checkpoint blockade. BMC Cancer. 2017;17:327.

    Article  Google Scholar 

  26. Manusow JS, Khoja L, Pesin N, Joshua AM, Mandelcorn ED. Retinal vasculitis and ocular vitreous metastasis following complete response to PD-1 inhibition in a patient with metastatic cutaneous melanoma. J Immunother Cancer. 2014;2:41.

    Article  Google Scholar 

  27. Van Den Brom RR, Abdulahad WH, Rutgers A, Kroesen BJ, Roozendaal C, deGroot DJ, et al. Rapid granulomatosis with polyangiitis induced by immune checkpoint inhibition. Rheumatology (Oxford). 2016;55:1143–5.

    Article  Google Scholar 

  28. Bender C, Dimitrakopoulou-Strauss A, Erik A, Hassel JC. Safety of the PD-1 antibody pembrolizumab in patients with high-grade adverse events under ipilimumab treatment. Ann Oncol. 2016;27:1353–4.

    Article  CAS  Google Scholar 

  29. Khoja L, Maruice C, Chappell M, MacMillan L, Al-Habeeb AS, Al-Faraidy N, et al. Eosinophilic fasciitis and acute encephalopathy toxicity from pembrolizumab treatment of a patient with metastatic melanoma. Cancer Immunol Res. 2016;4:175–8.

    Article  Google Scholar 

  30. Laubli H, Hench J, Stanczak M, Heijnen I, Papachristofilou A, Frank S, et al. Cerebral vasculitis mimicking intracranial metastatic progression of lung cancer during PD-1 blockade. J Immunother Cancer. 2017;5:46.

    Article  Google Scholar 

  31. Sun R, Danlos FX, Ammari S, Louvel G, Dhermain F, Champiat S, et al. Anti-PD-1 vasculitis of the central nervous system or radionecrosis? J Immunother Cancer. 2017;5:96.

    Article  Google Scholar 

  32. Volansky, R. Checkpoint checkmate: adverse event management for checkpoint inhibitors. Healio Rheumatology. 12/2018.

  33. Abdel-Wahab N, Shah M, Lopez-Olivio MA, et al. Use of immune checkpoint inhibitors in the treatment of patients with cancer and preexisting autoimmune disease: a systematic review. Ann Intern Med. 2017;168:121–30.

    Article  Google Scholar 

  34. Suarez-Almazor ME, Kim ST, Abdel-Wahab N, Diab A. Immune-related adverse events with use of checkpoint inhibitors for immunotherapy of cancer. Arthritis Rheum. 2017;69(4):687–99.

    Article  Google Scholar 

  35. Johnson DB, Sullivan RF, Ott PA, Carlino MS, Khushalani NI, Ye F, et al. Ipilimumab therapy in patients with advanced melanoma and preexisting autoimmune disorders. JAMA Oncol. 2016;2:234–40.

    Article  Google Scholar 

  36. Le Burel S, Champiat S, Mateus C, Marabelle A, Michot JM, Robert C, et al. Prevalence of immune-related systemic adverse events in patients treated with anti-programmed cell death 1/anti-programmed cell death ligand-1 agents: a single-centre pharmacovigilance database analysis. Eur J Cancer. 2017;82:34–44.

    Article  Google Scholar 

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Authors and Affiliations

  1. Division of Rheumatology, University of Mississippi Medical Center, 2500 N State St., Jackson, MS, 39216, USA

    Teresa M Crout, Day S Lennep, Shweta Kishore & Vikas Majithia

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  1. Teresa M Crout
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  2. Day S Lennep
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Correspondence to Teresa M Crout.

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Crout, T.M., Lennep, D.S., Kishore, S. et al. Systemic Vasculitis Associated With Immune Check Point Inhibition: Analysis and Review. Curr Rheumatol Rep 21, 28 (2019). https://doi.org/10.1007/s11926-019-0828-7

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