Orofacial adverse events associated with immune checkpoint inhibitors: using a large real-world dataset

Immune checkpoint inhibitors (ICIs) represent a promising therapeutic class in oncology, increasingly utilized either alone or alongside chemotherapy/radiotherapy. As their use expands, understanding the spectrum of oral adverse events especially when administered as monotherapy has become critical.

This retrospective study leveraged the TriNetX real-world healthcare dataset to identify patients treated solely with ICIs. We did not apply a specific time restriction for inclusion, to allow for the capture of all available patients who received ICIs. To identify patients on ICI monotherapy, we excluded those receiving concomitant chemotherapy or radiotherapy. Orofacial adverse events were categorized into xerostomia, oral mucosal disorders, and orofacial neural conditions.

Out of 15,638 patients meeting the inclusion and exclusion criteria, 1,564 (10%) developed orofacial immune-related adverse events (irAEs) following ICI administration. Among these, orofacial neuropathies accounted for 56.97%, oral mucosal disorders accounted for 33.95%, and xerostomia for 9.07%. The most prevalent orofacial irAE was dysphagia (3.6%), followed by facial numbness/trigeminal neuralgia (1.63%), oral lichenoid drug reaction (1.4%), stomatitis (1.22%), and xerostomia (0.91%).

This study highlights the adverse events associated with ICIs affecting the orofacial region. Our findings suggest that ICIs, even when used as a monotherapy, may contribute significantly to oral complications. Increased awareness and early identification of these complications is essential for timely management and improved patient quality of life.