Oral immune-related adverse events associated with PD-1 inhibitor treatment: a case series

Introduction: Immune Checkpoint Inhibitor (ICI) drugs have led to a revolution in the treatment of different forms of cancer, shifting the target of action from cancer cells to the patient’s immune system, enhancing their responses against the tumor itself. On the other hand, this mechanism can lead to responses against oneself, with the appearance of immune-related adverse events. The aim of the present study was to examine the immune-related adverse events (irAEs) affecting the mucous membranes of the oral cavity and the possible correlation between these and skin toxicities, which are reported in the literature as the most common adverse events. Materials and methods: Thirteen patients treated with anti-Programmed Death (PD-1) drugs (pembrolizumab, nivolumab, and cemiplimab) were selected. The data collected include the general history of the patient and the type of anticancer treatment. The sample was then analyzed by recording the alterations found on the mucous membranes of the oral cavity and on the skin. Finally, the average time that elapsed between the start of immunotherapy and the onset of lesions was analyzed. Results: Patients often had multiple lesions at the same time. Hyperkeratosis was found in three patients, candidiasis (pseudomembranous and median rhomboid glossitis) in two patients, epithelial atrophy in four patients, and ulcerative areas in two patients. One patient reported xerostomia with dysphagia. The anatomical areas most involved were the dorsal tongue and palate. Skin irAEs included skin rash erythema (n = 7) with diffuse redness, the presence of small bubbles with a crusty outcome, and dryness of the skin in the affected areas. Discussion: In the literature, there are few studies that analyze how irAEs affect the mucous membranes of the oral cavity in patients treated with ICI drugs. The most frequently described lesions are lichenoid reactions and xerostomia. Moreover, the development of mucositis, generally of low grade, has been reported. The present study has confirmed the data from the literature and, in addition, reports two cases of candidiasis, an adverse event that has never been shown in the literature. Conclusions: irAEs have the potential to affect any organ. The only way to avoid the occurrence of serious events that is currently available is early interception, which is only possible through the knowledge of these manifestations. It is therefore considered necessary to deepen our knowledge of oral irAEs and their correlation with dermatological toxicities, allowing for a multidisciplinary classification of the patient and a timely diagnosis of any adverse event and avoiding progression to more advanced stages, which could lead to the temporary or permanent suspension of anticancer drugs.