Oral side effects of immune checkpoint inhibitor therapy (ICIT): An analysis of 4683 patients receiving ICIT for malignancies at Massachusetts General Hospital, Brigham & Women's Hospital, and the Dana‐Farber Cancer Institute, 2011 to 2019

Abstract

Background Immune checkpoint inhibitors (ICIs) are increasingly accepted as a treatment option for several cancers. Although various systemic immune‐related adverse events (irAEs) have been characterized, the effect of ICIs on the oral cavity and contiguous structures is still poorly understood. Methods Electronic medical records of 4683 patients in the Mass General Brigham Registered Patient Data Registry who received ICI therapy (ICIT) between December 2011 and September 2019 were reviewed. Reports of oral conditions were categorized into oral mucosal disorders, xerostomia, and dysgeusia. After applying exclusion criteria, demographic characteristics and clinical features were summarized for the patients who had oral irAEs. Results In total, 317 patients developed oral conditions that were associated with ICIT (incidence, 6.8%; 317 of 4683 patients). These conditions included xerostomia (68.5%), oral mucosal disorders (33.4%), and dysgeusia (24.0%). In patients with oral irAEs, respiratory cancer (28.4%) was the most common primary cancer, followed by melanoma (26.2%), and head and neck cancer (14.8%). Oral mucosal disorders developed after the initiation of ICIT between 2 and 851 days (between 1 and 1332 days in patients with xerostomia and between 1 and 1455 days in patients with dysgeusia). Of all oral irAEs, 50.9% developed within 3 months, and 85.5% developed within 12 months. Conclusions Oral side effects appear to be more common among patients who receive ICIT than has been previously reported. Concomitant cytotoxic regimens may exacerbate the risk of oral adverse events, perhaps representing the sum of the effects of different, but simultaneous or sequential, pathogenic mechanisms. Additional studies are warranted to better characterize oral irAEs and their biologic basis.

The broadening scope of oral mucositis and oral ulcerative mucosal toxicities of anticancer therapies

“…In a meta‐analysis of 18 RCTs (n = 11,465 patients), 2.7% of patients experienced stomatitis, and 0.2% had severe OM‐irAEs 91 . In a retrospective study of 4683 ICI‐treated patients, 252 (5.4%) demonstrated mucosal lesions 92 . Of 8637 patients from a national insurance claims database, OM‐irAEs were reported in 1.5% of patients treated with ICIs 93 …”

“…8). The mean onset of oral irAEs is 3 months from the initiation of treatment, and most AEs occur within the first 12 months 92,94,95 . However, late onset has been reported, with toxicity developing more than a year after therapy.…”

“…These oral lichenoid reactions are usually asymptomatic and occur in an isolated manner, although they can be accompanied by skin, nail, or genital involvement 95 . Other reported inflammatory/antibody‐mediated mucosal manifestations include erythema multiforme‐like inflammation, pemphigoid, and Steven–Johnson syndrome 92,94,96‐100 . Immune‐mediated sialadenitis presenting with oral sicca is the second most common oral irAE reported in association with ICIs 101‐103 .…”

European recommendations for management of immune checkpoint inhibitors‐derived dermatologic adverse events. The EADV task force ‘Dermatology for cancer patients’ position statement

“…Oral irAEs are reported in about 7% of individuals under ICI treatment 88 but their overall incidence is probably Oral corticosteroids (0.5-1.0 mg/kg/day, l prednisolone) Consider a steroid-sparing agent †, ‡ Withhold or discontinue ICI † consider hospitalization until control of disease activity IV A…”

Oral manifestations of immune‐related adverse events in cancer patients treated with immune checkpoint inhibitors

“…Overall, irAEs have become increasingly well-recognized and well-characterized, but oral mucosal and salivary gland toxicities are less well-studied despite an estimated incidence of nearly 7% in patients treated with ICIs (Xu et al, 2021). This review summarizes the documented oral irAEs and proposes grading criteria and management guidelines.…”