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Case history

image A 59-year-old woman with renal cell carcinoma (RCC) presented to the medical oncology clinic. Three years previously she had undergone a radical nephrectomy for a T3N0M0 clear cell carcinoma. She had no history of autoimmune disease and had previously been otherwise fit.

She was initially treated with interleukin (IL)-2 therapy, but it was complicated by a C2 vertebral fracture, after which she proceeded to further treatment with sunitinib. An initially good partial response was maintained for 30 months despite two dose reductions due to toxicities. Restaging scans at 30 months found further disease progression and she commenced nivolumab therapy.

After two cycles of nivolumab the patient presented with sore, red, dry eyes (more so in the left, where her vision had reduced to 6/24 unaided, 6/12 pinhole) and polyarthropathy involving the small joints of the hands and wrists. Both eyes were erythematous on examination. An urgent ophthalmology review noted blepharitis, bilateral conjunctival injection, and a marked left corneal epitheliopathy consistent with acute dry eye. She was prescribed hourly preservative-free topical lubricants and a lubricating ointment for night-time.

Three weeks later her symptoms had not improved. Her vision had deteriorated to 6/36 unaided, 6/18 pinhole in the left eye, and an inferior corneal infiltrate was noted typical of marginal keratitis. A punctual plug was inserted into the left lower punctum; she was commenced on topical levofloxacin six times a day and topical steroids were added 4 days later. Two weeks later, oral prednisolone 30 mg/day was commenced for ongoing symptoms. The polyarthropathy improved rapidly and her ocular symptoms gradually resolved. The dose of oral prednisolone was steadily reduced over 6 weeks.

Re-challenge with nivolumab was discussed, but it was not possible as her performance status declined prior to recommencing treatment.

What is the evidence for nivolumab treatment in RCC?

What are the differential diagnoses in this case?

Which ocular and orbital toxicities may patients experience with immunotherapy treatments?

How are ocular toxicities graded?

What is the management of ocular and orbital toxicity with immunotherapy?

What is the evidence for nivolumab treatment in RCC?

Nivolumab is a fully humanized immunoglobulin G4 antibody against programmed death-ligand 1 (PD-L1). It is licensed in the UK for the management of metastatic disease in RCC and in multiple other cancer tumour sites, and the list continues to grow as further trials show positive data. Recent data of combination immune checkpoint therapy (ipilimumab and nivolumab) show benefit in first line treatment and may lead to a change in practice.1

The CheckMate 025 trial reported in 2015 was a multicentre, multinational phase II trial comparing nivolumab with everolimus as second line treatment. It demonstrated a median overall survival (OS) advantage of 25.0 months for nivolumab vs 19.6 months for everolimus (HR 0.73). Partial responses were seen in 24% of patients on nivolumab compared with 5% in those receiving everolimus, and a favourable toxicity profile: grades 3–4 ...

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