Clinical Characteristics and Outcomes of Oral Mucositis Associated With Immune Checkpoint Inhibitors in Patients With Cancer

Abstract

Background: Immune checkpoint inhibitor (ICI) therapy predisposes patients to immune-related adverse events (irAEs). Data are limited regarding the incidence, management, and outcomes of one such irAE: mucositis. In this study, we evaluated the clinical characteristics, disease course, treatment, and outcomes of ICI-mediated mucositis. Methods: This was a retrospective, single-center study of patients who received ICI therapy and developed oral mucositis at The University of Texas MD Anderson Cancer Center from January 2009 to September 2019. Inclusion criteria included age ≥18 years, a diagnosis of oral mucositis and/or stomatitis based on ICD-9 and ICD-10 codes, and therapy using CTLA-4 or PD-1/L1 inhibitors alone or combined with other agents. Results: We identified 152 patients with a mean age of 60 years, 51% of whom were men. Of the sample patients, 73% had stage IV cancer, with melanoma the most common (28%). Median time from ICI initiation to mucositis was 91 days. The most common clinical presentation of mucositis was odynophagia and/or oral pain (89%), 91% developed CTCAE grade 1–2 mucositis, and 78% received anti–PD-1/L1 monotherapy. Compared with anti–PD-1/L1–based therapy, anti–CTLA-4–based therapy was more frequently associated with earlier onset of mucositis (73 vs 96 days; P=.077) and a lower rate of symptom resolution (76% vs 92%; P=.029); 24% of patients required immunosuppressive therapy, which was associated with longer symptom duration (84 vs 34 days; P=.002) and higher mucositis recurrence rate (61% vs 32%; P=.006). ICI interruption was associated with worse survival (P=.037). Mucositis recurrence, immunosuppressant use, and presence of other irAEs did not affect survival. Conclusions: For ICI-mediated mucositis, a diagnosis of exclusion has not been well recognized and is understudied. Although the clinical symptoms of mucositis are mostly mild, approximately 25% of patients require immunosuppression. Mucositis recurrence can occur in approximately 39% patients. Our results showed that ICI interruption compromises overall survival.

CD5L-associated gene analyses highlight the dysregulations, prognostic effects, immune associations, and drug-sensitivity predicative potentials of LCAT and CDC20 in hepatocellular carcinoma

“…PD-1 and PD-L1 were two components in the programmed death-1 pathway and they were reported to be upregulated in the tumor microenvironment and could lead to immune suppression and tumor immune escape [87]. In many cancerous diseases [88][89][90][91], their inhibitors were reported to be effective to prolong the OS of the patients to some extent. Although many PD-1/L1 inhibitors have been approved for the treatment of advanced HCC, the efficiency is not satisfactory due to the heterogeneity of the patients [92][93][94].…”

Comparisons of Non-Oral Immune-Related Adverse Events Among Patients With Cancer With Different Oral Toxicity Profiles

“…This was higher than what was reported by Jacob et al, where 64% of patients with oral mucositis presented with other irAEs after the anti-CTLA-4 or anti-PD-1/PD-L1 treatment. 11 …”

Immune checkpoint inhibitors in cancer therapy: Review of orofacial adverse events and role of the oral healthcare provider

“…Integral to the management approach of oral mucosal irAEs is early and aggressive intervention with high-potency topical steroids [ 15 ]. Solution formulations work well for multifocal and/or hard to reach lesions, and gels can be applied to focal lesions with gauze or a cotton tip applicator.…”

“…Oral mucosal and salivary gland irAEs have been inconsistently reported and classified, so the prevalence is not clearly defined, though the incidence may be as high as seven percent [ 14 , 15 ]. They can occur with or without cutaneous or systemic manifestations [ 9 ].…”