A Case Report of Immune Checkpoint Inhibitor-Induced Aortitis Treated with Tocilizumab

Abstract

Vasculitic immune checkpoint inhibitor-related adverse events (irAEs) are rare, with limited data to guide their management. Here, we present a case of a 67-year-old female with stage IV cutaneous melanoma who received first-line pembrolizumab. She had completed 21 cycles of pembrolizumab dosed at 200 mg every 21 days over 15 months when she developed fatigue, chills, decreased appetite, night sweats, nausea, diarrhea, dry cough, and chest pain. A routine, staging positron emission tomography (PET) scan revealed aortitis of the transverse aortic arch. An extensive workup was unremarkable for other causes, so her condition was labeled a grade III immune-related vasculitis. Based on this diagnosis, we started high-dose prednisone and discontinued pembrolizumab. After two months of high-dose prednisone, she developed bothersome weight gain and insomnia, leading to a switch from prednisone to tocilizumab as a steroid-sparing agent. The selection of tocilizumab was based on its routine use for giant cell arteritis which can have extracranial symptoms including thoracic aortitis. Her symptoms resolved, and subsequent PET scans showed resolution of the aortitis and no evidence of metastatic melanoma. As the indications for immunotherapy expand, rare complications are becoming more prevalent, and more data will be needed to guide their management. While there is evidence for tocilizumab use as a steroid-sparing treatment for large-vessel vasculitides due to other conditions, this is the first case of its use to treat an aortitis irAE to our knowledge. In this case, it was an effective means of treating the patient while sparing them from prolonged corticosteroids.

Large‐vessel vasculitis induced by pegfilgrastim and immune checkpoint inhibitor in a patient with small‐cell lung cancer

“…Sato et al 11 reported a case of G‐CSF‐induced LVV with elevated serum IL‐6 levels, suggesting that IL‐6 is involved in the development of LVV. In contrast, ICIs have been shown to cause LVV as an immune‐related adverse event (irAE) 12,13 . ICI administration increases activated T‐cell infiltration into the vasculature and the levels of inflammatory cytokines, such as IL‐6, IL‐17, and interferon gamma, which may cause LVV 14 .…”

A cautionary note on pembrolizumab use in patients with ascending aortic aneurysms

“…The patient was subsequently switched to pembrolizumab without further aortic involvement. However, pembrolizumab has recently been linked to a case of transverse aortic arch aortitis [ 12 ] . Similar to the case presented here, the patient was undergoing treatment for metastatic melanoma.…”

“…High-dose steroids was started and pembrolizumab was discontinued. However, high-dose prednisolone cause bothersome weight gain and insomnia leading to a change from prednisolone to tocilizumab as a steroid-sparing agent [ 12 ] .…”

Rheumatic Immune-Related Adverse Events due to Immune Checkpoint Inhibitors—A 2023 Update

“…Vasculitis is classified into large-, medium-, and small-vessel types depending on blood vessel size [ 116 ], but ICIs can cause any type of vasculitis. In fact, giant cell arteritis (GCA) [ 117 , 118 ], aortitis and large-vessel involvement [ 119 , 120 , 121 ], IgA vasculitis [ 122 , 123 ], granulomatosis with polyangiitis [ 124 , 125 ], eosinophilic granulomatosis with polyangiitis [ 126 ], and cutaneous small-vessel vasculitis [ 127 , 128 ] have been reported after ICI administration. A retrospective pharmacovigilance study evaluated the association between ICIs and cardiovascular adverse events and demonstrated that ICI treatment was associated with a higher risk of vasculitis when compared with the database obtained from individual case safety reports [ 129 ].…”

“…Vasculitis caused by ICIs usually requires high-dose glucocorticoid treatment [ 77 ]. Other therapeutic options include cyclophosphamide [ 138 ], tocilizumab [ 119 ], rituximab [ 139 , 140 ], plasmapheresis [ 141 ], and JAK inhibitors [ 142 , 143 ]; however, the optimal management of ICI-induced vasculitis has not been established.…”