Management of pembrolizumab-induced steroid refractory mucositis with infliximab: A case report

Pembrolizumab is an anti-programmed death receptor 1 (PD-1) that was shown to have a tolerable safety profile with 17% of grade 3-4 drug-related adverse events, notable response rate of 16% with median duration of response of 8 mo, and median overall survival of 8 mo. Severe mucositis is a very rare complication with only two cases of grade 4 mucositis reported, and both cases had good response to intravenous methylprednisolone and subsequent oral prednisone tapering. We report the first case of pembrolizumab-induced severe mucositis that was refractory to steroid treatment.

An 80-year-old woman with a past medical history of recurrent right cheek nodular melanoma status post resection and new right lung metastatic melanoma on immunotherapy presented with dysphagia and odynophagia for 2 mo. She initially received 2 doses of ipilimumab 1 year ago with good outcome, but treatment was discontinued after developing severe diarrhea and rash. Pembrolizumab was then initiated 4 mo after disease progression. Significant improvement was noted after 3 doses. However, after 6 cycles of pembrolizumab, patient developed odynophagia and malnutrition. Improvement of symptoms was noted after discontinuation of pembrolizumab and initiation of steroids. 3 mo later, patient developed pharyngeal swelling with hoarseness and new oxygen requirement due to impending airway obstruction while being on prednisone tapering regimen, finally ended up with intubation and tracheostomy. Histologic analysis of left laryngeal and epiglottis tissue showed granulation tissue with acute on chronic inflammation, negative for malignancy and infection. Patient achieved marked improvement after 2 doses of infliximab of 5 mg/kg every 2 wk while continuing on prednisone tapering course.

We report the first case of pembrolizumab-induced grade 4 mucositis that had limited recovery with prolonged steroid course but had rapid response with addition of infliximab. The patient had recurrent mucositis symptoms whenever steroids was tapered but achieved complete response after receiving two doses of infliximab while continuing to be on tapering steroids. The success of infliximab in this patient with pembrolizumab-induced severe mucositis presents a potentially safe approach to reduce prolonged steroid course and accelerate recovery in managing this rare complication.