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Case history

image A 51-year-old woman with no significant medical history was diagnosed with stage IIIB (T2aN1aM0) V600D BRAF-mutant melanoma in 2012 after excision biopsy of a long-standing upper back lesion. Histology demonstrated a 1.7 mm non-ulcerated malignant melanoma. Wide local excision showed no evidence of residual disease. Sentinel lymph node biopsy identified one lymph node with isolated cells; she declined completion lymphadenectomy. The patient commenced regular ultrasound surveillance with her local team.

Unfortunately, 4 years later she developed a solitary 1.5 cm enlarged right axillary lymph node. Fine needle aspiration confirmed metastatic melanoma. A PET-CT scan excluded disease elsewhere. The patient underwent right axillary lymphadenectomy, which identified one 18 mm lymph node out of 22 replaced by tumour, with no evidence of extracapsular spread. She was then enrolled on to KEYNOTE-054, a randomized double-blind phase III study of adjuvant pembrolizumab vs placebo in resected high-risk melanoma.

After cycle 4 of treatment she developed grade 2 diarrhoea. Treatment was interrupted and a weaning regimen of oral prednisolone was commenced. After 12 weeks the diarrhoea resolved and study treatment was resumed. Symptoms recurred, however, after cycle 7. Treatment was stopped for a second time and a flexible sigmoidoscopy was done. Mild patchy erythema was seen and biopsies showed features in keeping with immunotherapy-associated colitis. Owing to recurrent toxicity the patient was taken off study in April 2017, oral steroids were adjusted and sulfasalazine was added. Later that month the patient was admitted to hospital with possible pneumonitis, adrenal insufficiency and sepsis, which were managed with steroid adjustment and antibiotics. Diarrhoea fluctuated over the course of 2017, and a further full colonoscopy performed in June 2017 identified similar features in keeping with immunotherapy-associated colitis. Gradually her symptoms settled and prednisolone was slowly weaned down.

Despite multiple immunotherapy-related toxicities, the patient made a full recovery and additional immunosuppression was not required. Steroids were discontinued in January 2018 and she remains disease-free with no evidence of metastatic disease to date.

What is the evidence for adjuvant immunotherapy in melanoma?

Which patients should be selected for adjuvant immunotherapy?

Was the decision to decline initial completion lymphadenectomy correct?

What are the patient's treatment options at relapse?

What is the evidence for adjuvant immunotherapy in melanoma?

Immunotherapy targeting programmed cell death protein 1 (PD-1) and cytotoxic T lymphocyte-associated protein 4 (CTLA-4) has been firmly established in patients with advanced melanoma.1,2 In more recent years the role of adjuvant immunotherapy in patients with completely resected high-risk stage III or IV disease has been explored, with positive results reported by three major randomized controlled trials (RCTs): Efficacy Study of Ipilimumab versus Placebo to Prevent Recurrence after Complete Resection of High Risk Stage III Melanoma (EORTC 18071);3 Efficacy Study of Nivolumab Compared to Ipilimumab in Prevention of Recurrence of Melanoma after Complete Resection of Stage IIIB/C or Stage IV Melanoma (CheckMate 238);4 and Study of Pembrolizumab (MK-3475) versus Placebo ...

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