Gastrointestinal Toxicities of Immune Checkpoint Inhibitors Are Associated With Enhanced Tumor Responsiveness and Improved Survival.

Background: Immune checkpoint inhibitors (ICIs) are increasingly used to treat advanced malignancies. However, they are associated with the development of multiple gastrointestinal immune-related adverse events (GI-irAEs). We aimed to evaluate the types and severity of GI-irAEs associated with ICI therapy, to identify potential risk factors for developing GI-irAEs and to determine the relationship of GI-irAEs development to tumor responsiveness and overall survival. Methods: All patients who received ICIs for advanced malignancies at our center were included. Medical records were reviewed, and data extraction included: baseline demographic characteristics, immunotherapy regimens, development of GI-irAEs, response to treatment, and overall survival. Overall survival was calculated from the date of treatment initiation and estimated by the Kaplan-Meier method. Results: Five hundred sixty-seven patients received ICI therapy for stage IV malignancies. Forty-one (7%) patients experienced at least one GI-irAE. Among those experiencing GI-irAEs, 23 (56%) developed hepatitis, 17 (42%) developed colitis, four (10%) developed pancreatitis, and two (5%) developed gastritis. Patients who developed GI-irAEs experienced a better response to ICI therapy compared to patients who did not develop GI-irAEs (41% vs. 27%, P = 0.003). The 2-year overall survival rate of stage IV cancer patients who developed GI-irAEs was 62% (95% confidence interval (CI): 49 - 79) and 36% for those who did not develop GI-irAEs (95% CI: 32 - 41) (P = 0.002). The median follow-up time of surviving patients was 28 months. Twelve (29%) of the patients receiving dual ICI therapy developed GI-irAEs. Conclusion: Hepatitis, colitis, and pancreatitis were the most commonly encountered GI-irAEs with ICI therapy. Development of these GI-irAEs was associated with superior tumor responsiveness and better overall survival.

Endocrine Toxicity and Outcomes in Patients With Metastatic Malignancies Treated With Immune Checkpoint Inhibitors.

CONTEXT: Immune checkpoint inhibitors (ICIs) have gained a revolutionary role in management of many advanced malignancies. However, immune-related endocrine events (irEEs), have been associated with their use. irEEs have nonspecific clinical presentations and variable timelines, making their early diagnosis challenging. OBJECTIVE: To identify risk factors, timelines, and prognosis associated with irEEs development. DESIGN AND SETTING: Retrospective observational study within the Cleveland Clinic center. PATIENTS: Metastatic cancer adult patients who received ICIs were included. METHODS: 570 charts were reviewed to obtain information on demographics, ICIs used, endocrine toxicities, cancer response to treatment with ICI, and overall survival. MAIN OUTCOME MEASURES: Incidence of irEEs, time to irEEs development and overall survival of patients who develop irEEs. RESULTS: The final cohort included 551 patients. The median time for the diagnosis of irEEs was 9 weeks. Melanoma was associated with the highest risk for irEEs (31.3%). Ipilimumab appeared to have the highest percentage of irEEs (29.4%), including the highest risk of pituitary insufficiency (11.7%), the most severe (Grade 4 in 60%) and irreversible (100%) forms of irEEs. Forty-five percent of patients with irEEs had adequate cancer response to ICI compared to 28.3% of patients without irEEs (P = 0.002). Patients with irEEs had significantly better survival compared to patients without irEEs (P < 0.001). CONCLUSIONS: In the adult population with metastatic cancer receiving treatment with ICI, irEEs development may predict tumor response to immunotherapy and a favorable prognosis. Ipilimumab use, combination ICI therapy, and melanoma are associated with a higher incidence of irEEs.

Prevalence and Predictors of Gastrointestinal Dysmotility in Patients with Hypermobile Ehlers-Danlos Syndrome: A Tertiary Care Center Experience.

Introduction Ehlers-Danlos syndrome (EDS), specifically the hypermobility type (hEDS), is associated with a variety of gastrointestinal (GI) conditions. This study aims to evaluate the prevalence of and factors associated with gut dysmotility in patients with hEDS. Methods This is a retrospective study of hEDS patients conducted at the Cleveland Clinic's Center for Personalized Genetic Healthcare between January 2007 and December 2017. Demographics, GI motility testing, endoscopic, and imaging data were extracted from the patients' charts. Results A total of 218 patients with hEDS were identified. Among them, 136 (62.3%) patients had at least one GI symptom at the time of EDS diagnosis. Motility testing was performed and reported in 42 (19.2%) patients. Out of them, five (11.9%) had esophageal dysmotility, 18 (42.8%) had gastroparesis, five (11.9%) had small bowel/colon altered transit time, and four (9.5%) had global dysmotility. In univariable analysis, patients with postural orthostatic tachycardia syndrome (POTS) [odds ratio (OR): 8.88, 95% CI: 3.69-24.9, p<0.0001], fibromyalgia (OR: 4.43, 95% CI: 2.04-10.1, p=0.0002), history of irritable bowel syndrome (OR: 5.01, 95% CI: 2.31-11.2, p<0.0001), and gastroesophageal reflux disease (OR: 3.33, 95% CI: 1.55-7.44, p=0.002) were more likely to be diagnosed with GI dysmotility. On multivariable analysis, only POTS (OR: 5.74, 95% CI: 2.25-16.7, p=0.0005) was significantly associated with an increased likelihood of GI dysmotility. Conclusions This study suggests that GI symptoms are relatively common among patients with hEDS. Of the patients tested for dysmotility, 76.2% were found to have some form of dysmotility. POTS was found to be an independent predictive factor for GI dysmotility.

Interventions to Decrease Overuse of Cardiac Monitoring (Telemetry) When Transitioning from the Intensive Care Unit to the Regular Nursing Floor.

Background Cardiac monitoring (telemetry) is a common over-utilized hospital resource in the United States. Previous studies have shown that telemetry does not improve outcomes for low-risk patients. Inappropriate utilization occurs because of lack of awareness of guideline-based indications or non-adherence to known indications. Objective A quality improvement study was conducted to reduce telemetry overutilization during the transition of care from the intensive care unit (ICU) by 15% through increasing awareness of indications for telemetry. Methods The study cohort included patients originally admitted to the ICU for sepsis who had improved and were stable for transfer to a non-ICU setting. Subjects were identified and included during pre-intervention (six weeks) and intervention (six weeks) periods. Resident physicians and nurse practitioners were targeted using multiple modalities of education: didactic lectures during week one, poster demonstrations during week three, and video presentations during week five. Results A total of 246 study subjects during the pre-intervention and 94 study subjects in the intervention period were studied; 187 of the 246 subjects in the pre-intervention arm (76%) and 58 of the 94 subjects in the intervention arm (61.7%) were transferred with telemetry. Telemetry utilization dropped by 23.1% at the end of the intervention period. Conclusion Educating the caregivers about the indications for telemetry led to a decrease in over-utilization of telemetry on the transition of care from the ICU to the regular nursing floor. Repetitive and multi-modality educational interventions were effective tools and associated with increased adherence to established guidelines for telemetry usage.