Clinical characteristics, management, and prognosis of pembrolizumab-induced immune-related oral mucositis.

[BACKGROUND] Pembrolizumab-induced immune-related oral mucositis (irOM) is a rare and often underrecognized toxicity. This study aimed to systematically characterize its clinical profile, histopathologic patterns, management strategies, and outcomes to support timely diagnosis and evidence-based care.

[METHODS] A comprehensive search of PubMed, EMBASE, Web of Science, WanFang Data, and CNKI was performed using a combination of MeSH terms (e.g., "Pembrolizumab," "Oral Mucositis," "Stomatitis," "Mucous Membrane Pemphigoid," and "Immune-Related Adverse Events") and free-text terms (e.g., "anti-PD-1" and "checkpoint inhibitor toxicity"), with Boolean operators (AND/OR) applied to maximize retrieval; reports published up to July 31, 2025, were included. The quality of case reports was evaluated using the JBI Critical Appraisal Checklist.

[RESULTS] Among 18 patients, the median age was 72 years (range 15, 88) and 72.2% were male. The median onset of irOM was 24 weeks (range 3, 66), consistent with a delayed presentation. Clinically, painful oral ulcers or erosions were most frequently observed (50.0%), followed by dysphagia or odynophagia (27.8%). Histopathologic evaluation most often revealed a pemphigoid-like pattern (27.8%) or mixed inflammatory infiltrates (22.2%), with additional findings including ulceration with granulation tissue, lichenoid mucositis, plasma cell infiltrates, and epithelial hyperplasia. Systemic corticosteroids were the mainstay of therapy (88.9%), while pembrolizumab was discontinued in one-third of cases (33.3%). Refractory disease occasionally required immunomodulatory agents such as methotrexate (16.7%) or infliximab (11.1%). Clinical outcomes were generally favorable, with 88.9% of patients achieving symptomatic improvement or remission and a median recovery time of 6 weeks (range 2, 52). On rechallenge, 3 of 4 patients had no recurrence.

[CONCLUSION] Pembrolizumab-induced irOM usually develops after months of treatment, presenting as ulcerative mucositis, sometimes extending to the airway or esophagus. Biopsy may show pemphigoid-like changes. Corticosteroids are effective, and immunosuppressants can be used for refractory cases. Recovery is typically within weeks and rechallenge is feasible for select patients.