Citations

e16488 Background: Small bowel adenocarcinoma (SBA) and ampullary adenocarcinoma (ampullary AC) are rare gastrointestinal (GI) malignancies. Treatment strategies are largely extrapolated from colorectal cancer, where oxaliplatin-based regimens are the most common first-line therapy in advanced disease. Although bevacizumab is considered safe in metastatic SBA, its efficacy remains unproven, and evidence is limited to small retrospective studies. We assessed the association of adding bevacizumab to FOLFOX with survival and toxicity in a large real-world cohort. Methods: We conducted a retrospective cohort study using the TriNetX Global Collaborative Network (January 2000-December 2025), including data from 105 healthcare organizations. Adults (≥18 years) with SBA or ampullary AC treated with FOLFOX with or without bevacizumab were identified. Cohorts were propensity score-matched on age, sex, race, comorbidities, and metastatic sites. Outcomes included overall mortality, GI perforation, bleeding, venous thromboembolism (VTE), hospital admission, and emergency department (ED) visits. Kaplan-Meier and Cox proportional hazards models were used for time-to-event analyses. Results: After matching, 818 patients were included in each cohort. In the FOLFOX + bevacizumab cohort, mean age was 66.1 ± 12.0 years and 53.8% were male; 63.7% were White, 13.8% Black, 5.6% Asian, 12.0% Unknown/Other, and 4.4% Hispanic/Latino. Over a median follow-up of 13 months, FOLFOX + bevacizumab was associated with higher overall mortality compared with FOLFOX alone (55.3% vs 45.2%; HR 1.24 [95% CI 1.1-1.4]; p = 0.002) and shorter median OS (15.1 vs 19.5 months). Rates of GI perforation (15.5% vs 16.7%; HR 0.90 [95% CI 0.71-1.15]; p = 0.39), GI bleeding (13.1% vs 13.6%; HR 0.96 [95% CI 0.73-1.25]; p = 0.74), and VTE (19.1% vs 21.4%; HR 0.88 [95% CI 0.71-1.09]; p = 0.23) were similar between groups. Hospital admissions were higher in the FOLFOX + bevacizumab cohort (2.8% vs 1.3%; HR 2.1 [95% CI 1.0-4.3]; p = 0.04). Findings were consistent at 5-year follow-up. Conclusions: In this real-world cohort, the addition of bevacizumab to FOLFOX was not associated with improved survival and was associated with higher healthcare utilization. Prospective, disease-specific studies are needed to define its role in this population. Outcomes at median 13-month follow-up after propensity matching (FOLFOX + bevacizumab vs FOLFOX). Outcome % vs % HR p Overall mortality 55.3 vs 45.2 1.24 0.002 Hospital admission 2.8 vs 1.3 2.1 0.04 ED visit 45.2 vs 42.4 1.02 0.75 GI perforation 15.5 vs 16.7 0.90 0.39 GI bleeding 13.1 vs 13.6 0.96 0.74 VTE 19.1 vs 21.4 0.88 0.23

7548 Background: Glucagon-like peptide-1 (GLP-1) receptor agonists are widely used for the treatment of type 2 diabetes and obesity, and emerging evidence suggests their benefits beyond glycemic control, including cardiovascular effects and potential anti-inflammatory and anti-proliferative properties. Therapeutic advances in multiple myeloma (MM) have improved the overall life-expectancy in our patients. However, metabolic comorbidities remain common, likely driven by disease burden, functional decline, ongoing inflammation, and treatment related effects. Our study evaluates the impact of GLP-1 receptor agonists on outcomes in patients with MM, exploring potential interactions between metabolic modulation and disease outcomes. Methods: We conducted a real-world retrospective cohort study using the TriNetX Global Collaborative Network, covering January 2000 to December 2025, encompassing data from 168 global healthcare organizations. Patients aged 18 and above with multiple myeloma were identified and then stratified into two groups based on treatment with GLP-1 agonists or not. The two groups were then propensity-matched based on age, sex, race, and various comorbidities. We assessed outcomes including overall mortality, myocardial infarction (MI), ischemic stroke, sepsis, anemia, pancreatitis, venous thromboembolism (VTE), and ED visits. Time-to-event analyses were performed using Kaplan-Meier methods and Cox proportional hazards models. Results: We identified 1716 patients with MM and obesity who received GLP-1 receptor agonists, and 13,491 patients with MM and obesity who did not receive GLP-1 therapy. After propensity matching, each cohort consisted of 1712 patients with well-balanced baseline characteristics. We followed these patients for 5 years from treatment initiation. Patients with MM who received GLP-1 had a significantly lower risk of overall mortality (Hazard Ratio [HR]: 0.423, 95% CI: 0.351-0.509, p-value <0.001), MI (Risk Difference [RD]: -3.6 %, 95% CI: -5.4 % to -1.7 %, p-value <0.001), ischemic stroke (RD: -1.7 %, 95% CI: -3.3 % to -0.1 %, p-value = 0.04), sepsis with and without shock (RD: -3.0 %, 95% CI: -4.9 % to -1.1 %, p-value = 0.002), and anemia (RD: -9.6 %, 95% CI: -12.9 % to -6.4 %, p-value <0.001). There was no statistically significant difference in the rates of VTE, ED visits, and pancreatitis between the two cohorts. Conclusions: Our study revealed that patients with MM with obesity who received GLP-1 therapy had significantly lower rates of overall mortality, MI, ischemic stroke, sepsis with and without shock, and anemia. Additional longitudinal cohort studies are required to explore the associations between these agents and inform clinical practice guidelines in these patients.

5543 Background: Glucagon-like peptide-1 (GLP-1) receptor agonists are widely used for the treatment of type 2 diabetes and obesity. Emerging evidence suggests that these agents may have potential anti-tumor activity as GLP-1 signaling may influence pathways involved in cell proliferation and inflammation. Endometrial cancer is the most common gynecologic malignancy, and obesity represents a well-established, modifiable risk factor that may adversely affect oncologic outcomes through chronic inflammation and metabolic dysregulation. Our study aims to evaluate the impact of GLP-1 receptor agonists on outcomes among patients with endometrial cancer and comorbid obesity. Methods: A retrospective cohort study was conducted using the TriNetX Global Collaborative Network, covering January 2000 to December 2025, encompassing data from 168 global healthcare organizations. Patients aged 18 and above with endometrial cancer and comorbid obesity were identified and then stratified into two groups based on treatment with GLP1 agonists or not. The two groups were then propensity-matched based on age, ethnicity, medical comorbidities, and stage of cancer. Outcomes were assessed for five years from treatment initiation and included overall mortality, myocardial infarction (MI), ischemic stroke; development of peritoneal, lymph node, and visceral metastases; sepsis, pancreatitis, and ED visits. Time-to-event analyses were performed using Kaplan-Meier methods and Cox proportional hazards models. Results: After propensity matching, 6352 patients were included in each cohort with balanced baseline characteristics. Our analysis found that patients with endometrial cancer and comorbid obesity who received GLP-1 agonists had a significantly lower risk of overall mortality (Hazard Ratio [HR]: 0.45, 95% CI: 0.39-0.51, p-value <0.001), development of peritoneal metastases (Risk Difference [RD]: -2.16%, 95% CI: -2.74% to -1.58%, p-value <0.001), nodal metastases (RD: -0.41%, 95% CI: -0.72% to -0.09%, p-value =0.01), visceral metastases (RD: -3.76%, 95% CI: -4.60% to -2.93%, p-value =0.01), and sepsis with and without shock (RD: -1.42%, 95% CI: -2.14% to -0.70%, p-value <0.001) compared to patients who did not receive GLP-1 agonists. There was no statistically significant difference in the rates of MI, ischemic stroke, ED visits, and pancreatitis between the two cohorts. Conclusions: In this large real-world analysis, patients with endometrial cancer and comorbid obesity who received GLP-1 agonists had lower rates of overall mortality; peritoneal, lymph node, and visceral metastases, and sepsis with or without shock. Additional longitudinal cohort studies are imperative to explore the associations between these agents and inform clinical practice guidelines in this patient population.

Abstract Introduction Acute chest syndrome (ACS) is a life-threatening complication of sickle cell disease that often requires hospitalization and urgent intervention. Hospitalized patients may present with multiple acute conditions necessitating glucocorticoid therapy. Although glucocorticoids are well known for their anti-inflammatory effects, their use in ACS remains controversial due to concerns about worsening of underlying infection, progression to sepsis, and subsequent respiratory failure. This study aims to evaluate the impact of concomitant glucocorticoid use on clinical outcomes in patients with ACS. Methods A retrospective cohort study was conducted using the US Collaborative Network TriNetX, covering January 2000 to December 2023, encompassing data from 105 global healthcare organizations. Adult patients aged 18 and above with acute chest syndrome were identified and then stratified into two groups based on treatment with glucocorticoids during the index hospitalization or not. The two groups were then propensity-matched based on age, sex, race, and comorbidities. We followed these patients for 5 years to assess outcomes, including overall mortality, simple transfusions, exchange transfusions, need for mechanical ventilation, incidence of pneumonia, influenza, sepsis without shock, sepsis with shock, and need for hemodialysis. Results We identified 4197 patients in the acute chest syndrome with glucocorticoids cohort and 8211 patients in the acute chest syndrome without glucocorticoids cohort. After propensity matching, each cohort consisted of 4111 patients with similar baseline characteristics. Our analysis found that over 5 years, patients with acute chest syndrome who received glucocorticoids during the index hospitalization had a significantly higher risk of overall mortality (Hazard Ratio (HR): 1.361, 95% CI: 1.158 to 1.599, p-value &lt;0.001), simple transfusions (HR: 2.191, 95% CI: 2.015 to 2.381, p-value =0.009), exchange transfusions (Risk difference: 0.008, 95% CI: 0.003 to 0.013, p-value =0.001), need for mechanical ventilation (Risk difference: 0.024, 95% CI: 0.016 to 0.032, p-value &lt;0.001), pneumonia (HR: 1.190, 95% CI: 1.111 to 1.276, p-value =0.004), influenza (Risk difference: 0.044, 95% CI: 0.029 to 0.059, p-value &lt;0.001), sepsis without shock (Risk difference: 0.016, 95% CI: 0.007 to 0.024, p-value &lt;0.001), and sepsis with shock (Risk difference: 0.026, 95% CI: 0.018 to 0.034, p-value &lt;0.001). There was no statistically significant difference in the need for hemodialysis between the two subgroups. Conclusion Our study found that patients with acute chest syndrome who were exposed to glucocorticoids during the index hospitalization had a significantly increased risk of overall mortality, simple transfusions, exchange transfusions, need for mechanical ventilation, incidence of pneumonia, influenza, sepsis without shock, and sepsis with shock. Further longitudinal cohort studies are imperative to better understand these associations and guide evidence-based clinical practice in this population.

Abstract INTRODUCTION: Bruton tyrosine kinase inhibitors (BTKis) are becoming the preferred treatment for patients with chronic lymphocytic leukemia (CLL), taking the place of novel chemoimmunotherapies. While these medications significantly improve both progression-free and overall survival, they are also linked to various adverse effects, including cardiovascular toxicity. In contrast, glucagon-like peptide-1 (GLP-1) agonists have shown benefits for patients with diabetes mellitus who are at high risk for cardiovascular disease. Studies indicate that these drugs not only improve glycemic control but also lead to a reduction in the incidence of major cardiovascular events. This study aimed to assess the incidence of cardiovascular events and overall survival among CLL patients receiving BTK inhibitors who were also taking GLP-1 agonists for diabetes mellitus and/or obesity, compared to diabetic or obese CLL patients on BTK inhibitors not receiving GLP-1 agonists. METHODS: We utilized the TriNetX Global Collaborative Network to identify patients with CLL who are being treated with BTKis such as ibrutinib, acalabrutinib, or zanubrutinib, and who also had diabetes mellitus and/or obesity. Cohorts were formed based on the use of GLP-1 agonists. Propensity score matching was performed to adjust for potential confounders, including age, gender, ethnicity, alcohol consumption, tobacco use, diabetes mellitus, obesity, hypertension, and end-stage renal disease. Outcomes such as all causes of mortality, atrial fibrillation/flutter, acute heart failure, and acute ischemic heart disease were evaluated within one year of initiating GLP-1 agonist therapy. Risk differences (RD), risk ratios (RR), and 95% confidence intervals (CIs), were calculated. Kaplan-Meier survival analysis was performed, and the log-rank test was used to compare survival probability between groups. A p-value &lt; 0.05 was considered statistically significant. RESULTS: A total of 844 patients with CLL were included in the study, with 422 patients in each propensity-matched cohort. The incidence of atrial fibrillation/atrial flutter was significantly lower among patients receiving concurrent BTKis and GLP-1 agonists compared to those on BTKis alone (12.08% vs. 17.29%; RD –5.21%; p= 0.03; RR 0.699, 95% CI: 0.502% to 0.973%). Kaplan–Meier analysis demonstrated a significantly lower cumulative incidence of atrial fibrillation/atrial flutter at 365 days in the GLP-1 agonist cohort compared to non-users (log-rank test, p = 0.0245), indicating a higher atrial fibrillation–free survival probability among GLP-1 users. There were no statistically significant differences between groups in the incidence of ischemic heart disease (27.48% vs. 23.46%; RD 4.08%; p= 0.17; RR 1.172, 95% CI: 0.929% to 1.477%) or heart failure (13.27% vs. 13.27%; RD 0%; p= 1; RR 1, 95% CI: 0.708% to 1.412%). Although not statistically significant, a trend toward lower all-cause mortality was observed in patients receiving concurrent BTK inhibitors and GLP-1 agonists compared to those on BTK inhibitors alone (4.976% vs. 8.294%; risk difference –3.31%; p = 0.052; relative risk 0.6, 95% CI: 0.355 to 1.013; Kaplan–Meier analysis, log-rank test p = 0.055). A large cohort is needed to confirm this last finding. CONCLUSION: The use of GLP-1 agonists was associated with a significantly reduced incidence of atrial fibrillation/atrial flutter and a trend toward improved overall survival in diabetic or obese CLL patients receiving BTK inhibitors. These findings suggest a potential cardioprotective effect of GLP-1 agonists in this high-risk population. However, further prospective cohort studies or randomized controlled clinical trials are needed to confirm these observations.

Abstract Introduction Glucagon-like peptide-1 (GLP-1) receptor agonists are widely used for the treatment of type 2 diabetes and obesity. Emerging evidence suggesting their potential anti-inflammatory and anti-proliferative effects as well as cardiovascular benefits. Chronic myeloid leukemia (CML), a myeloproliferative neoplasm, has seen major therapeutic advances with tyrosine kinase inhibitors (TKIs). However, metabolic comorbidities remain widely prevalent in these patients due to both cancer-associated risk factors and the effects of therapy. Our study aims to evaluate the impact of GLP-1 receptor agonists on outcomes among patients with CML, exploring potential interactions between metabolic modulation and disease behaviour. Methods A retrospective cohort study was conducted using the US Collaborative Network TriNetX, covering January 2000 to December 2023, encompassing data from 105 global healthcare organizations. Adult patients aged 18 and above with CML and comorbid obesity were identified and then stratified into two groups based on treatment with GLP-1 agonists or not. The two groups were then propensity-matched based on age, sex, race, and comorbidities. We followed these patients for 5 years to assess outcomes, including overall mortality, myocardial infarction, ischemic stroke, sepsis, and need for mechanical ventilation and hemodialysis. Results We identified 701,767 patients with CML and obesity who received GLP-1 receptor agonists, and 6,811,928 patients with CML and obesity who did not receive GLP-1 therapy. After propensity matching, each cohort consisted of 700,998 patients with similar baseline characteristics. Our analysis found that over 5 years, patients with CML and obesity who received GLP-1 receptor agonists had a significantly lower risk of overall mortality (Hazard Ratio (HR): 0.509, 95% CI: 0.501 to 0.518, p-value &lt;0.001), myocardial infarction (HR: 0.785, 95% CI: 0.769 to 0.801, p-value &lt;0.001), ischemic stroke (HR: 0.665, 95% CI: 0.632 to 0.700, p-value &lt;0.001), hemodialysis (HR: 0.445, 95% CI: 0.430 to 0.461, p-value &lt;0.001) and sepsis (HR: 0.726, 95% CI: 0.714 to 0.738, p-value &lt;0.001). There was no statistically significant difference in the need for mechanical ventilation between the two subgroups. Conclusion Our study revealed that patients with CML and obesity who received GLP-1 receptor agonists had a significantly lower risk of mortality, myocardial infarction, ischemic stroke, hemodialysis and sepsis. Further longitudinal cohort studies are warranted to better understand these associations and inform clinical practice guidelines.