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Case history

image A 72-year-old Caucasian woman with locally advanced sinonasal mucosal malignant melanoma (MMM) received combination immunotherapy. She had initially presented with apparent nasal polyps, which were resected but which were shown to be melanoma on pathological review. Imaging showed extensive malignancy involving the left nasal cavity and ethmoid sinus with extension into the maxillary sinus. Multidisciplinary team discussion confirmed her malignancy was inoperable and she was referred to the medical oncology team for consideration of systemic therapy.

Mutational analysis showed no evidence of a BRAF V600 mutation in the tumour and she was commenced on combination cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) immune checkpoint inhibitor (ICPI) therapy with ipilimumab and nivolumab.

After three cycles of combination therapy she experienced mild fatigue and was found to have isolated adrenal impairment with hypocortisolaemia. Her pituitary axes remained intact. Given her minimal symptoms, she received hydrocortisone replacement and continued with immunotherapy. An initial CT scan after four cycles of combination immunotherapy showed a significant reduction in the size of the left nasal tumour to practical resolution. Given her stability on hormone replacement and response to therapy, she progressed to maintenance single-agent nivolumab.

Following one cycle of single-agent therapy (five ICPI cycles in total) the patient became acutely unwell with nausea, dizziness and confusion. On admission to hospital she was found to have unrecordably high blood glucose with significant acidosis and a high lactate. She was diagnosed with diabetic ketoacidosis and managed according to acute protocols. She was admitted to the ITU and improved within 24 h. She was discharged from hospital after a 5 day stay having been started on long-term basal–bolus insulin therapy. Given how unwell she had been with multiple immune-related adverse events (irAEs), she did not receive any further ICPI treatment and commenced active surveillance.

Follow-up imaging a year after commencing ICPIs showed a complete response to treatment. A subsequent scan 10 months after discontinuation of therapy, however, suggested mild thickening on the left sinonasal cavity, confirmed as recurrence on an interval MRI scan. The patient underwent surgical resection of the recurrent melanoma with planned consolidation radiotherapy.

This patient experienced an initial response to combination immunotherapy, with a period of complete response amounting to 15 months of disease control. Furthermore, she underwent surgical resection following ICPI therapy despite initially having inoperable disease.

What is the clinical landscape in MMM?

What is the role of ICPIs in MMM?

What endocrinopathies can be caused by ICPIs?

What is the recommended management of diabetes secondary to ICPI therapy?

What is the clinical landscape in MMM?

MMM arises in the epithelial lining of multiple organs. It is rare, accounting for ∼1% of the total melanoma population. In contrast to cutaneous melanoma (CM), the incidence of MMM over the last decade has been stable.1 There is a female predominance and the median age of onset is 70 years (although MMM ...

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