Jake Jacob, MD1, Barbara E. Dutra, MD2, Victor Garcia-Rodriguez, MD2, Kavea Panneerselvam, MD1, Fiyinfoluwa O. Abraham, MD2, Fangwen Zou, MD3, Petros Grivas, MD, PhD4, John Thompson, MD4, Anusha Shirwaikar Thomas, MD5, Yinghong Wang, MD, PhD5; 1Baylor College of Medicine, Houston, TX; 2University of Texas Health Science Center, Houston, TX; 3University of Texas MD Anderson Cancer Center, Houton, TX; 4University of Washington, Seattle, WA; 5University of Texas MD Anderson Cancer Center, Houston, TX
Introduction: Increased use of immune checkpoint inhibitors (ICI) for cancer therapy has led to a rise in immune-related adverse events (irAEs), including toxicity of the gastrointestinal tract. Mucositis is one such irAE for which there is limited data. This study aims to evaluate the clinical characteristics, disease course, treatment, and outcome of ICI-related mucositis. Methods: This is a retrospective, single center study of 152 adult patients (pts) who received ICI therapy and developed oral mucositis at MD Anderson Cancer Center from January 2009 to September 2019. ICD 9 and10 codes for mucositis and/or stomatitis were used to identify eligible pts. Baseline, demographic and oncology related data were collected. Statistical analysis to determine the association between measured variables and overall survival was performed using RStudio (v 1.0.136) and SPSS24. Results: In our cohort of 152 patients, the mean age was 60 (±14) years and 51% were men. The most common cancer type was melanoma (28%), with 73% having stage IV disease. The median time to onset of mucositis from ICI initiation was 97 days; 33 (22%) received CTLA-4 monotherapy or combination with PD-1/L1, and 119 (78%) received PD-1/L1 monotherapy. Anti-CTLA-4 based therapy was more frequently associated with earlier onset of mucositis (72 vs 96 days, p=0.077), lower rate of symptom resolution (18% vs 40%, p=0.032) compared to PD-1/L1 monotherapy. The most common clinical presentation of mucositis was odynophagia and/or oral pain (90%). Most patients (91%) developed CTCAE grade 1-2 mucositis; of the 36 (25%) patients that required immunosuppression, we note the presence of a longer symptom duration (84 vs 34 days, p=0.002) and higher recurrence rate (61% vs 32%, p=0.006) compared to those patients not needing immunosuppression (Table 2). Interruption of ICI treatment was associated with shorter overall survival (OS)(p=0.037) compared to continued ICI treatment through mucositis. Mucositis recurrence, immunosuppressant use, and presence of other irAEs were not associated with OS. Discussion: Mucositis associated with ICI has not been well recognized and is under-studied. The diagnosis requires the exclusion of other common etiologies related to cancer treatment. Clinical symptoms are mostly mild, however up to 25% in our cohort required immunosuppressant therapy. Mucositis recurrence can be up to 38%. Interruption of ICI treatment is associated with shorter OS.
Table 1. Clinical characteristics of mucositis based on the type of ICI therapy (N=152). Abbreviations: ICI, immune checkpoint inhibitor; IQR, interquartile range; SD, standard deviation. CTLA-4containing therapy included CTLA-4 monotherapy (16 cases) and combination of CTLA-4 and PD-1/L1 agents (17 cases).
Table 2. Clinical characteristics and outcomes of mucositis stratified by Immunosuppressant treatment (N=152). 22 patients used systemic immunosuppressants only, 7 used topical only, and 7 used both topical and systemic immunosuppressants. Agents include: IV Methylprednisolone, PO Dexamethasone, PO Prednisone, Topical Dexamethasone, topical fluocinonide
Figure 1. Overall Survival in association with immune checkpoint inhibitor termination(A) and recurrence of mucositis (B)
Disclosures: Jake Jacob indicated no relevant financial relationships. Barbara Dutra indicated no relevant financial relationships. Victor Garcia-Rodriguez indicated no relevant financial relationships. Kavea Panneerselvam indicated no relevant financial relationships. Fiyinfoluwa Abraham indicated no relevant financial relationships. Fangwen Zou indicated no relevant financial relationships. Petros Grivas indicated no relevant financial relationships. John Thompson indicated no relevant financial relationships. Anusha Shirwaikar Thomas indicated no relevant financial relationships. Yinghong Wang indicated no relevant financial relationships.