Severe immune mucositis and esophagitis in metastatic squamous carcinoma of the larynx associated with pembrolizumab

Fanny Zulay Acero Brand, Nicolas Suter, Jean-Philippe Adam, Bernard Faulques, Antonio Maietta, Denis Soulières, Normand Blais

Pembrolizumab is an anti-programmed death 1 (PD-1) receptor monoclonal antibody that has shown activity as second line treatment for metastatic head and neck squamous cell carcinoma (HNSCC). Immune-related adverse events are now well described complications of PD-1 inhibitors and most organ sites have been shown to be potentially affected. We describe a 69-year old patient with a relapsed squamous cell carcinoma of the supraglottic larynx with lung metastasis after receiving adjuvant concurrent cisplatin and radiotherapy. This patient was treated with pembrolizumab and benefitted from therapy with major radiological improvement of disease. After 14 cycles of pembrolizumab 200 mg IV each 3 weeks, he experienced dysphagia that evolved to a grade 4 oral cavity and pharynx mucositis and esophagitis. Histologic analysis showed ulcerative esophagitis associated with granulation tissue. Pembrolizumab was discontinued and IV methylprednisolone 2 mg/kg/day was initiated. Two days later, the patient reported a 50% recovery in his symptoms which were completely resolved after 2 weeks. Methylprednisolone was switched to oral prednisone and a taper was planned over 8 weeks. During the fourth week of taper, the patient presented recurrence of grade 1 oral mucositis. Prednisone was increased 2 mg/kg/day for 2 weeks followed by slower tapering over a period of 5 months. Pembrolizumab was not reinitiated. This is the first described case of grade 4 immune mucositis and esophagitis associated with pembrolizumab. Because the use of pembrolizumab is increasing in oncology, pharmacists and physicians should be aware of this rare manifestation.