Oral immune-related adverse events associated with PD-1 and PD-L1 inhibitor therapies: A retrospective, single-institution study

Summary: Immune checkpoint inhibitors of key programmed cell death 1 (PD-1) and its ligand (PD-L1) are efficacious cancer treatments through augmentation of T-cell mediated tumor destruction. Despite extensive research published on this drug class, there is a paucity of literature describing oral immune-related adverse events (irAEs), which generally occur in less than 10% of patients. Our study aims to characterize the clinical presentation, treatments, and outcomes of patients with oral irAEs on PD-1/PD-L1 inhibitors. We conducted a retrospective chart review including patients on PD-1 (nivolumab, pembrolizumab, cemiplimab) and PD-L1 (atezolizumab, avelumab, durvalumab) inhibitors who were treated with dexamethasone elixir, viscous lidocaine, or magic mouthwash. Patients with oral irAEs that could be attributed to chemotherapy or radiation therapy, or with a history of head and neck carcinomas were excluded to avoid confounding. Descriptive characteristics were collected for 29 patients. Mean age was 63.5 years, and 62.1% patients were female. Most of our patients were Hispanic/Latino (48.3%) and on pembrolizumab (65.5%). 37.9% of patients were concurrently on chemotherapy, 24.1% on targeted cancer therapy, and 34.5% on PD-1/PDL-1 monotherapy. A majority of their cancers did not respond to immunotherapy (55.2%). The mean number of PD-1/PD-L1 doses before oral irAEs appeared was 6.7; the mean number of days before oral irAEs was 223.9. Clinically, the most common description of the oral irAE was mucositis, stomatitis, or ulceration (n=19), then xerostomia (n=11), then color changes (n=6). The most common oral anatomic sites for the irAE were the mucosa (n=12) and tongue (n=9). Four patients had oral biopsies showing ulcerated mucosa with granulation tissue, amyloidosis, and two results with lichenoid mucositis. The results of this study may help clinicians with early identification and management of oral adverse events from PD-1/PD-L1 inhibitors and raise awareness of this important association. Jasmine H. Wong¹, Sharen Rivas¹, Janet Choi¹, Xin Wang¹, Lana Salloum¹, Shaun Wu¹, Solbie Choi¹, Shaynie Segal¹, Rebecca Goldberg¹, Beth N. McLellan¹ 1. Montefiore Medical Center, New York, NY, United States. Clinical Research: Epidemiology and Observational Research