Since the first approval of immune checkpoint inhibitors (ICIs) in 2011, these agents have rapidly become an integral treatment option across tumor types. However, with the increased adoption of ICIs, the incidence of immune-related adverse events (irAEs) continues to rise, and rare toxicity continues to be reported. Here, we present a case of a 70-year-old male patient with widespread metastatic melanoma who developed rapid onset anasarca and transaminitis after initiation of dual anti-PD-1/CTLA-4 inhibition with nivolumab and ipilimumab. An extensive workup was performed with serologies returning positive for anti-tissue transglutaminase immunoglobulin (tTG-IgA) and endoscopy revealing duodenal mucosal atrophy with duodenal biopsies confirming celiac disease. All symptoms resolved after initiation of a gluten-free diet without the addition of immunosuppression. This case highlights the importance of considering celiac disease in patients with suspected protein-losing enteropathy on ICI, the fulminant nature this uncommon irAE can present with, and underscores the broad differential clinicians must maintain when managing presumed irAEs.
Background Immune checkpoint inhibitors (ICI) are associated with a distinct spectrum of toxicities. Data on irAE hospitalization rates and clinical course of patients with thoracic malignancies are lacking. Methods Patients with advanced thoracic malignancy treated with ICI (2/2016 -6/2021) were retrospectively identified. Demographic and clinical data of confirmed irAE hospitalizations were extracted from the medical record and a descriptive analysis was performed. ResultsFrom February 2016 to June 2021, 1,312 patients with thoracic malignancy received ICI (monotherapy, combination with 2nd ICI or other agents) with 102 patients (7.7%) hospitalized for irAEs . Treatment intent was first-line therapy with ICI in most patients (N= 50, 49%) and adjuvant ICI in 9% (N =9). 59% (N =60) received ICI alone, 32% (N =33) chemo plus immunotherapy, and 7% (N =7) dual ICI. The average age on admission was 68 years in both genders. The median time between ICI initiation and admission was 64 days (1-935). The most common evidenced irAEs were pneumonitis (N = 38, 37%), hepatitis (N = 20, 20%), myocarditis (N = 14, 14%) and colitis (N = 13, 13%). Nearly half (N = 18, 47%) of patients with pneumonitis were treated with prior thoracic radiation and received first line (N = 22, 58%) ICI. Pneumonitis cases had the highest 60-day readmission rate (37%, N = 14) with a 60-day mortality rate of 53% (N = 20). 60-day re-admission and mortality rates were 19% (N = 17) and 29% (N = 26), respectively, among the rest of the cohort. Multi-organ toxicity occurred in 36% (N = 37) of patients. Myocarditis patients often had a concomitant irAE (79%; 11/14) with 36% (N = 5) presenting overlapping neuromuscular toxicity. Overall, 64% (N = 65) received IV corticosteroids for a median duration of 42.5 days (0-527) and 18% (N = 18) required second line immunosuppression. irAEs solved to grade 1 or less after immunosuppression in 63 patients. Seven patients (7%) experienced a grade 5 event while admitted. ICI rechallenge occurred in 14 patients. Median OS was 360 days; (16 -2219, table 1). Conclusions Severe irAE requiring inpatient admission, though infrequent, results in considerable morbidity, mortality, and healthcare utilization. Pneumonitis was the most common irAE requiring inpatient management in our lung cancer population with a significant risk of mortality despite the use of guideline-directed systemic immunosuppression. This study highlights the continued need for prospective research to optimally manage severe toxicities, particularly pneumonitis. Ethics Approval The study obtained IRB approval.Protocol #: 2017P000501.
Purpose: This study aims to describe the global landscape of clinical research into interventions for gastroesophageal (GE) cancers, which are a leading cause of cancer morbidity and mortality worldwide. We examine trial characteristics, focusing on geographic distribution of trial sites, participation of low-and-middle-income countries (LMICs), and factors associated with premature trial termination. Methods: We queried ClinicalTrials.gov database to identify all completed or terminated Phase III interventional studies investigating GE cancers (esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC), gastroesophageal junctional (GEJ) and gastric adenocarcinoma). All reported characteristics were extracted. Pearson’s chi-square and Fisher’s exact test were used to compare differences in completed and terminated trials. Multivariate logistic regression was used to determine predictors of termination. Results: A total of 179 trials were identified; 90% were therapeutic. Most included sites in Asia (61%), Europe (32%), and North America (23%); few included sites in South America (9%), Africa (4%), and Oceania (9%). 63% of trials included high-income countries (HICs) sites alone; only 7% included sites in lower-middle or low-income countries. Most (70%) focused exclusively on gastric or GEJ adenocarcinoma, 13% on EAC and ESCC, and 9% ESCC alone. 16% (n=29) of trials terminated, most due to accrual difficulties (n=13, 44%). In multivariate analysis, study site number, location, and eligible patient population emerged as predictors of termination. Trials conducted exclusively in the US were more likely to terminate (OR 7.22 [95% CI 1.59-32.69]). Conversely, trials conducted exclusively in LMICs were less likely to terminate (OR 0.04 [95% CI 0.01-0.59] v conducted in HIC alone). Studies on ESCC were more likely to terminate (OR 17.74 [95%CI 1.49-210.69]). Trial design characteristics, intervention characteristics, and funding sources were not associated with termination. Conclusion: Although 80% of GE malignancies occur in LMICs, trial activity disproportionately occurs in HICs. Few trials focus on EAC/ESCC despite being highly fatal, highlighting an unmet need. Geographic location of trial sites emerged as a predictor of trial termination, with studies involving LMICs sites less likely to terminate prematurely. This finding highlights the potential benefit of including LMICs in future clinical trials to advance research for these diseases. Citation Format: Ayo Falade, Oluwatayo Adeoye, Geoffrey Buckle. Clinical Trials in Gastroesophageal Cancers: An Analysis of the Global Landscape of Interventional Trials From ClinicalTrials.gov [abstract]. In: Proceedings of the 11th Annual Symposium on Global Cancer Research; Closing the Research-to-Implementation Gap; 2023 Apr 4-6. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(6_Suppl):Abstract nr 21.
Aims: The relationship between appendectomy and immune checkpoint inhibitor (ICI) enterocolitis was explored. Methods: Patients who began ICIs between July 2010 and September 2020 (n = 10,907) were included. The exposure group included patients with evidence of appendectomy prior to ICIs in operative notes (n = 380). The control group included patients with evidence of normal appendix in radiologic reports (n = 3602). ICI enterocolitis was defined as histopathologic evidence of colitis or enteritis attributed to ICIs. The association between appendectomy and ICI enterocolitis was characterized by multivariate logistic regression. Results: 248 patients (6.2%) developed ICI enterocolitis. The odds of ICI enterocolitis were similar among those with prior appendectomy and those without appendectomy (adjusted odds ratio: 0.82; 95% CI: 0.49–1.36; p = 0.449). Conclusion: No association was found between prior appendectomy and ICI enterocolitis.
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