Skip to main content
Top
Published in: Acta Neurologica Belgica 2/2020

01-04-2020 | Myasthenia Gravis | Original article

Myositis as a neuromuscular complication of immune checkpoint inhibitors

Authors: Lynn Vermeulen, Christophe E. Depuydt, Petra Weckx, Oliver Bechter, Philip Van Damme, Dietmar R. Thal, Kristl G. Claeys

Published in: Acta Neurologica Belgica | Issue 2/2020

Login to get access

Abstract

Immune checkpoint inhibitors (ICI) induce improved clinical outcomes associated with numerous cancers, but immune-related adverse events can occur, including neuromuscular complications. We searched for all muscle biopsies from the patient data system of University Hospitals Leuven (UZ Leuven) from January 2014 to July 2018 (n = 686) and collected clinical data of patients with a biopsy-proven ICI-related myositis and expanded the pathological examinations. We identified three cases of ICI-related myositis in patients with malignant melanoma. The clinical phenotype ranged from mild to life threatening. Two patients had a myositis–myasthenia gravis overlap syndrome and one had a co-occurring myocarditis. Pathological examination showed a necrotizing and/or inflammatory myopathy with CD4 + and CD8 + T cells and CD68 + macrophages. IgG staining was positive in all cases. PD-1 and PD-L1 reactions were negative for inhibitors of the PD-1/PD-L1 pathway (nivolumab, atezolizumab) and positive for CTLA-4 inhibitors (ipilimumab). With increasing usage of ICI, clinicians must be aware of rare but potentially serious adverse events such as myositis. Early detection by inquiring about complaints and clinical signs of weakness and monitoring the creatine phosphokinase level in serum are recommended. Our histological findings are in line with other reports. The IgG positivity suggests a local role of the ICI in the pathophysiology of the myositis. Further research must be performed to identify patients at risk and to optimize treatment of the complications.
Literature
1.
go back to reference Kreamer KM (2014) Immune checkpoint blockade: a new paradigm in treating advanced cancer. J Adv Pract Oncol 5(6):418–431PubMedPubMedCentral Kreamer KM (2014) Immune checkpoint blockade: a new paradigm in treating advanced cancer. J Adv Pract Oncol 5(6):418–431PubMedPubMedCentral
3.
go back to reference Hodi FS, O'Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC, Akerley W, van den Eertwegh AJ, Lutzky J, Lorigan P, Vaubel JM, Linette GP, Hogg D, Ottensmeier CH, Lebbe C, Peschel C, Quirt I, Clark JI, Wolchok JD, Weber JS, Tian J, Yellin MJ, Nichol GM, Hoos A, Urba WJ (2010) Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 363(8):711–723. https://doi.org/10.1056/NEJMoa1003466 CrossRefPubMedPubMedCentral Hodi FS, O'Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC, Akerley W, van den Eertwegh AJ, Lutzky J, Lorigan P, Vaubel JM, Linette GP, Hogg D, Ottensmeier CH, Lebbe C, Peschel C, Quirt I, Clark JI, Wolchok JD, Weber JS, Tian J, Yellin MJ, Nichol GM, Hoos A, Urba WJ (2010) Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 363(8):711–723. https://​doi.​org/​10.​1056/​NEJMoa1003466 CrossRefPubMedPubMedCentral
11.
go back to reference Touat M, Maisonobe T, Knauss S, Ben Hadj Salem O, Hervier B, Aure K, Szwebel TA, Kramkimel N, Lethrosne C, Bruch JF, Laly P, Cadranel J, Weiss N, Behin A, Allenbach Y, Benveniste O, Lenglet T, Psimaras D, Stenzel W, Leonard-Louis S (2018) Immune checkpoint inhibitor-related myositis and myocarditis in patients with cancer. Neurology 91(10):e985–e994. https://doi.org/10.1212/WNL.0000000000006124 CrossRefPubMed Touat M, Maisonobe T, Knauss S, Ben Hadj Salem O, Hervier B, Aure K, Szwebel TA, Kramkimel N, Lethrosne C, Bruch JF, Laly P, Cadranel J, Weiss N, Behin A, Allenbach Y, Benveniste O, Lenglet T, Psimaras D, Stenzel W, Leonard-Louis S (2018) Immune checkpoint inhibitor-related myositis and myocarditis in patients with cancer. Neurology 91(10):e985–e994. https://​doi.​org/​10.​1212/​WNL.​0000000000006124​ CrossRefPubMed
12.
13.
go back to reference Hunter G, Voll C, Robinson CA (2009) Autoimmune inflammatory myopathy after treatment with ipilimumab. Can J Neurol Sci 36(4):518–520CrossRef Hunter G, Voll C, Robinson CA (2009) Autoimmune inflammatory myopathy after treatment with ipilimumab. Can J Neurol Sci 36(4):518–520CrossRef
17.
go back to reference Mitchell EL, Lau PKH, Khoo C, Liew D, Leung J, Liu B, Rischin A, Frauman AG, Kee D, Smith K, Brady B, Rischin D, Gibson A, Mileshkin L, Klein O, Weickhardt A, Arulananda S, Shackleton M, McArthur G, Ostor A, Cebon J, Solomon B, Buchanan RR, Wicks IP, Lo S, Hicks RJ, Sandhu S (2018) Rheumatic immune-related adverse events secondary to anti-programmed death-1 antibodies and preliminary analysis on the impact of corticosteroids on anti-tumour response: a case series. Eur J Cancer 105:88–102. https://doi.org/10.1016/j.ejca.2018.09.027 CrossRefPubMed Mitchell EL, Lau PKH, Khoo C, Liew D, Leung J, Liu B, Rischin A, Frauman AG, Kee D, Smith K, Brady B, Rischin D, Gibson A, Mileshkin L, Klein O, Weickhardt A, Arulananda S, Shackleton M, McArthur G, Ostor A, Cebon J, Solomon B, Buchanan RR, Wicks IP, Lo S, Hicks RJ, Sandhu S (2018) Rheumatic immune-related adverse events secondary to anti-programmed death-1 antibodies and preliminary analysis on the impact of corticosteroids on anti-tumour response: a case series. Eur J Cancer 105:88–102. https://​doi.​org/​10.​1016/​j.​ejca.​2018.​09.​027 CrossRefPubMed
20.
go back to reference Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, Schadendorf D, Dummer R, Smylie M, Rutkowski P, Ferrucci PF, Hill A, Wagstaff J, Carlino MS, Haanen JB, Maio M, Marquez-Rodas I, McArthur GA, Ascierto PA, Long GV, Callahan MK, Postow MA, Grossmann K, Sznol M, Dreno B, Bastholt L, Yang A, Rollin LM, Horak C, Hodi FS, Wolchok JD (2015) Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med 373(1):23–34. https://doi.org/10.1056/NEJMoa1504030 CrossRefPubMedPubMedCentral Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, Schadendorf D, Dummer R, Smylie M, Rutkowski P, Ferrucci PF, Hill A, Wagstaff J, Carlino MS, Haanen JB, Maio M, Marquez-Rodas I, McArthur GA, Ascierto PA, Long GV, Callahan MK, Postow MA, Grossmann K, Sznol M, Dreno B, Bastholt L, Yang A, Rollin LM, Horak C, Hodi FS, Wolchok JD (2015) Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med 373(1):23–34. https://​doi.​org/​10.​1056/​NEJMoa1504030 CrossRefPubMedPubMedCentral
28.
31.
go back to reference Brahmer JR, Lacchetti C, Schneider BJ, Atkins MB, Brassil KJ, Caterino JM, Chau I, Ernstoff MS, Gardner JM, Ginex P, Hallmeyer S, Holter Chakrabarty J, Leighl NB, Mammen JS, McDermott DF, Naing A, Nastoupil LJ, Phillips T, Porter LD, Puzanov I, Reichner CA, Santomasso BD, Seigel C, Spira A, Suarez-Almazor ME, Wang Y, Weber JS, Wolchok JD, Thompson JA (2018) National Comprehensive Cancer Network 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(17):1714–1768. https://doi.org/10.1200/JCO.2017.77.6385 CrossRefPubMedPubMedCentral Brahmer JR, Lacchetti C, Schneider BJ, Atkins MB, Brassil KJ, Caterino JM, Chau I, Ernstoff MS, Gardner JM, Ginex P, Hallmeyer S, Holter Chakrabarty J, Leighl NB, Mammen JS, McDermott DF, Naing A, Nastoupil LJ, Phillips T, Porter LD, Puzanov I, Reichner CA, Santomasso BD, Seigel C, Spira A, Suarez-Almazor ME, Wang Y, Weber JS, Wolchok JD, Thompson JA (2018) National Comprehensive Cancer Network 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(17):1714–1768. https://​doi.​org/​10.​1200/​JCO.​2017.​77.​6385 CrossRefPubMedPubMedCentral
35.
go back to reference Johnson DB, Balko JM, Compton ML, Chalkias S, Gorham J, Xu Y, Hicks M, Puzanov I, Alexander MR, Bloomer TL, Becker JR, Slosky DA, Phillips EJ, Pilkinton MA, Craig-Owens L, Kola N, Plautz G, Reshef DS, Deutsch JS, Deering RP, Olenchock BA, Lichtman AH, Roden DM, Seidman CE, Koralnik IJ, Seidman JG, Hoffman RD, Taube JM, Diaz LA Jr, Anders RA, Sosman JA, Moslehi JJ (2016) Fulminant myocarditis with combination immune checkpoint blockade. N Engl J Med 375(18):1749–1755. https://doi.org/10.1056/NEJMoa1609214 CrossRefPubMedPubMedCentral Johnson DB, Balko JM, Compton ML, Chalkias S, Gorham J, Xu Y, Hicks M, Puzanov I, Alexander MR, Bloomer TL, Becker JR, Slosky DA, Phillips EJ, Pilkinton MA, Craig-Owens L, Kola N, Plautz G, Reshef DS, Deutsch JS, Deering RP, Olenchock BA, Lichtman AH, Roden DM, Seidman CE, Koralnik IJ, Seidman JG, Hoffman RD, Taube JM, Diaz LA Jr, Anders RA, Sosman JA, Moslehi JJ (2016) Fulminant myocarditis with combination immune checkpoint blockade. N Engl J Med 375(18):1749–1755. https://​doi.​org/​10.​1056/​NEJMoa1609214 CrossRefPubMedPubMedCentral
40.
go back to reference Coutzac C, Adam J, Soularue E, Collins M, Racine A, Mussini C, Boselli L, Kamsukom N, Mateus C, Charrier M, Cassard L, Planchard D, Ribrag V, Fizazi K, Loriot Y, Lepage P, Scoazec JY, Robert C, Carbonnel F, Chaput N (2017) Colon immune-related adverse events: anti-CTLA-4 and anti-PD-1 blockade induce distinct Immunopathological entities. J Crohns Colitis 11(10):1238–1246. https://doi.org/10.1093/ecco-jcc/jjx081 CrossRefPubMed Coutzac C, Adam J, Soularue E, Collins M, Racine A, Mussini C, Boselli L, Kamsukom N, Mateus C, Charrier M, Cassard L, Planchard D, Ribrag V, Fizazi K, Loriot Y, Lepage P, Scoazec JY, Robert C, Carbonnel F, Chaput N (2017) Colon immune-related adverse events: anti-CTLA-4 and anti-PD-1 blockade induce distinct Immunopathological entities. J Crohns Colitis 11(10):1238–1246. https://​doi.​org/​10.​1093/​ecco-jcc/​jjx081 CrossRefPubMed
44.
go back to reference Simonaggio A, Michot JM, Voisin AL, Le Pavec J, Collins M, Lallart A, Cengizalp G, Vozy A, Laparra A, Varga A, Hollebecque A, Champiat S, Marabelle A, Massard C, Lambotte O (2019) Evaluation of readministration of immune checkpoint inhibitors after immune-related adverse events in patients with cancer. JAMA Oncol. https://doi.org/10.1001/jamaoncol.2019.1022 CrossRefPubMed Simonaggio A, Michot JM, Voisin AL, Le Pavec J, Collins M, Lallart A, Cengizalp G, Vozy A, Laparra A, Varga A, Hollebecque A, Champiat S, Marabelle A, Massard C, Lambotte O (2019) Evaluation of readministration of immune checkpoint inhibitors after immune-related adverse events in patients with cancer. JAMA Oncol. https://​doi.​org/​10.​1001/​jamaoncol.​2019.​1022 CrossRefPubMed
Metadata
Title
Myositis as a neuromuscular complication of immune checkpoint inhibitors
Authors
Lynn Vermeulen
Christophe E. Depuydt
Petra Weckx
Oliver Bechter
Philip Van Damme
Dietmar R. Thal
Kristl G. Claeys
Publication date
01-04-2020
Publisher
Springer International Publishing
Published in
Acta Neurologica Belgica / Issue 2/2020
Print ISSN: 0300-9009
Electronic ISSN: 2240-2993
DOI
https://doi.org/10.1007/s13760-020-01282-w

Other articles of this Issue 2/2020

Acta Neurologica Belgica 2/2020 Go to the issue