Oral immune‐related adverse events associated with PD‐1 inhibitor therapy: A case series

Abstract

Objective The aim of this study was to characterize clinical and histopathological features, and management outcomes of patients with oral immune‐related adverse events (irAEs) secondary to programmed cell death‐1 (PD‐1) inhibitors. Methods This was a case series of cancer patients receiving PD‐1 inhibitor therapy who were referred to oral medicine for the development of oral irAEs. Demographic, clinical, and histopathological data were collected from electronic medical records. Results There were 13 patients (7 males) with a median age of 68 years (range: 39–82) who were treated with nivolumab (n = 7) or pembrolizumab (n = 6). Oral irAEs included lichenoid lesions (n = 10), erythema multiforme (EM) (n = 2), and acute graft‐versus‐host disease reactivation (n = 1), with or without ulcerations (n = 8). Four patients (31%) presented with only oral irAEs. Oral biopsies showed lichenoid mucositis (n = 4). Management with topical and systemic steroids led to complete symptomatic response in most patients (n = 12). PD‐1 inhibitor therapy was temporarily discontinued (n = 3) and discontinued indefinitely (n = 2) due to severe oral irAEs. Conclusion Patients receiving PD‐1 inhibitors may develop oral irAEs characterized by lichenoid lesions, ulcers, or EM. Topical and systemic steroids appear to be effective in managing oral lesions although the severity of irAEs may necessitate PD‐1 inhibitor therapy dose modification.

Leukoplakia and Immunology: New Chemoprevention Landscapes?

“…administration, risk of high-grade toxicities, and high cost of PD-1 antibodies, could be limited [112]. Additionally, patients receiving PD-1 inhibitors may develop oral immune-related adverse events characterized by lichenoid lesions, ulcers, or erythema multiforme [113]. Moreover, other classes of targeted anti-cancer therapies with immunologic activities as mTOR inhibitors are known to induce stomatitis.…”

Approach to the aphthous lesions of the oral mucosa

“…1 FDE may present as ulcerative aphthous stomatitis of the oral mucosa. 43 Immune checkpoint inhibitor-associated oral mucositis, erosions, and ulcerations 44 , Mammalian (mechanistic) target of rapamycin (mTOR) inhibitorassociated stomatitis (mIAS) 45 , and nicorandilinduced oral ulcerations 46 have also been reported in the literature.…”

Oral Immune-Related Adverse Events – Current Concepts and their Management

“…[ 6 ] Various oral adverse reactions, especially mucositis, are frequently reported in patients undergoing PD-1 inhibitor therapy. [ 10 ] Majority of the irAEs are mild and reversible immune reactions, but sometimes, they can progress to fatal conditions. These adverse reactions have major clinical implications.…”

“…Few of those cases developed severe oral ulcerations that required discontinuation and alteration in the PD-1 inhibitor therapy. [ 10 ] Dermal Lichenoid reactions without involvement of mucosal membranes are reported in about 25% of undergoing ICI therapy. [ 45 ] Intraoral lesions can be managed with topical corticosteroids.…”

“…Toxicities of Grades 1 and 2 do not require alteration in the ICI therapy, but Grades 3 and 4 toxicities require alteration or discontinuation of the ICI therapy along with specialist consultation. [ 10 ]…”