Oral toxicities associated with immune checkpoint inhibitors: A retrospective cohort study

Abstract Background: Oral toxicities associated with immune checkpoint inhibitor (ICI) therapy are increasingly reported. However, the characteristics of clinical, histopathological presentation, and treatment outcome remain poorly defined. Objectives: To comprehensively characterize the clinical presentation, histopathology features, treatment patterns, and cancer outcome of ICI-associated oral toxicities. Methods: We retrospectively reviewed patients diagnosed with ICI-associated oral toxicities from the Chang Gung Memorial Hospital system and Taipei Veterans General Hospital, Taiwan, between 2015 and 2023. Clinical data, histopathologic findings, treatment, and tumor response were systematically analyzed. Results: Thirty-five patients developed oral toxicities following ICI therapy. Eighteen patients (51.4%) presented with mucositis, ten (28.6%) with oral lichen planus (LP), and seven (20.0%) with oral involvement of Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). The mean latency to onset time of oral toxicities was 77.6 days after ICI therapy initiation. Most patients improved with systemic and/or topical corticosteroid. Around 80% had concurrent cutaneous or systemic immune-related adverse events. However, ICI therapy was interrupted in 13 patients (37.1%). One patient with SJS/TEN died during the acute stage. Overall, around sixty percent of the enrolled patients achieved a partial or complete tumor response or stable disease. Conclusion: Mucositis and LP were the predominant ICI-associated oral toxicities. Oral manifestations of SJS/TEN, although less common, carried significant morbidity and mortality. Prompt recognition and appropriate management are critical to minimize complications and maintain oncologic benefit. Larger prospective studies are needed to refine risk prediction and optimize care.