- 03/2021 amelanotic melanoma, BRAF wild type
- 09/2021: Lung metastasis, complete resection
- pT4bN0M1c, IV (AJCC 2017)
- 10/2021 – 11/2021 Immunotherapy with nivolumab 240 mg every 2 weeks (adjuvant)
- 02/2022 – 03/2022 Immunotherapy with nivolumab 240 mg every 2 weeks (adjuvant)
- 04/2022 – 05/2022 Immunotherapy with nivolumab 240 mg every 2 weeks (adjuvant)
After 1 month of adjuvant therapy with nivolumab, the patient presented with fever, myalgia without CK elevation, arthralgia and elevated inflammatory parameters. Due to a suspected systemic inflammatory reaction, most likely due to the immunotherapy, the nivolumab therapy was paused and the patient received methylprednisolone 1 mg/kg bw with subsequent taper. Shortly after resuming immunotherapy, the patient presented again with elevated inflammatory parameters, a hyperinflammatory syndrome was suspected, but the patient also described stabbing pains in his left eyebrow and ear. Nivolumab was re-initiated again, and shortly thereafter the patient complained of recurrent amaurosis fugax in the right eye. Duplex sonography showed the typical findings of a giant cell arteritis of the temporal artery. We initiated a therapy with prednisolone 1 mg/kg bw.
In summary, the patient showed laboratory signs of inflammation, fever, myalgia and arthralgia, temporal headaches and recurrent amaurosis fugax. In retrospect, the initial myalgia may be interpreted as a sign of polymyalgia rheumatica, and the stabbing pain in eyebrow and ear as a sign of arteritis temporalis.
We initiated therapy with prednisolone 1 mg/kg bw. The additional administration of tocilizumab is planned. To date, the patient has shown no recurrence of the melanoma.
A continuation of immunotherapy may be discussed after a detailed benefit-risk assessment but is currently not planned.
Giant cell arteritis (GCA) is an inflammatory autoimmune disease of large blood vessels; histology shows a granulomatous inflammatory reaction with fused macrophages (“giant cells”). Symptoms are variable and include e.g. headache, difficulty opening the mouth, flu-like symptoms, double vision and amaurosis fugax, fever, weight loss, and polymyalgia. GCA is frequently associated with polymyalgia rheumatica and has an approximately 20% risk of blindness.
GCA is a rare side effect of immunotherapy. An analysis of VigiBase revealed 18 cases of temporal GCA, 55% of the cases occurred after anti-CTLA4 therapy and one third of the cases were accompanied by visual impairment or blindness (Salem et al, Lancet Oncol., 2018). Two case reports described GCA under anti-PD1 therapy (Narala et al., Am J Ophthalmol Case Rep., 2020; Betrains et al., J Clin Rheumatol., 2021); in both cases, immunotherapy was discontinued and the patients treated with steroids. Therapy of ICI-induced GCA may also include methotrexate or tocilizumab (Heinzerling et al., Dtsch Arztebl., 2019). Evidence supports an important role of PD-1 and CTLA-4 pathways in the pathophysiology of vasculitis (Zhang et al., Proc Natl Acad Sci, 2017).
Giant cell arteritis is a rare side effect of immune checkpoint inhibitors that physicians should be aware of. In the case of typical systemic symptoms, headaches or vision disturbances, a low-threshold GCA clarification should be carried out.
