Syal, Arshi

402 Background: Trastuzumab deruxtecan (T-DXd) is a HER2-targeted antibody-drug conjugate (ADC) with a cytotoxic payload. TDXd was approved in 2021 to be used in advanced gastric or GEJ cancers. Although given the recent approval, real-world evidence on efficacy and safety is limited. We sought to evaluate the efficacy and safety of T-DXd through a combined meta-analysis of clinical trials and real-world studies. Methods: A comprehensive search was conducted across PubMed, Embase, Scopus, and Clinicaltrials.gov databases. The original studies evaluating T-DXd in patients with metastatic/recurrent gastric/gastroesophageal junction (GEJ) cancers were included in the analysis. The pooled objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and the incidence of adverse events (AEs) were analyzed. A random-effects model was used for meta-analysis, and the heterogeneity of the data was evaluated by Chi-sq Q test and the I 2 statistic using OpenMeta [Analyst] (Tufts Medical Center, Boston, MA, USA). Results: This meta-analysis incorporated 8 studies (3 phase II clinical trials, 5 retrospective studies) comprising 915 patients with advanced HER2-positive gastric/GEJ cancer. The median patient age was 66.5 years (range: 27–89), with 75.4% males, 70.4% Asian, and 29.0% Caucasians. 77.9% had an ECOG performance status of 0–1, while 21.8% had ECOG ≥2. Histologically, 53.6% had intestinal and 22.9% diffuse-type adenocarcinoma. HER2 overexpression (IHC3+) was observed in 75.8% of evaluable cases, and 22.4% were IHC2+/FISH positive. 77.6% had primary gastric and 22.4% GEJ tumors. The median line of therapy was 3 (range: 2–11), with prior immune checkpoint inhibitor use in 31.8% and prior surgery in 44.5% .The pooled ORR was 47.7% (95% CI 43.0-52.4%) and DCR was 82.50% (79.40%–85.72%); PFS and OS were 4.92 and 9.86 months, respectively. Safety analysis revealed grade ≥3 AEs in 48.2% of patients, neutropenia (24.5%) being the most common. Treatment discontinuation due to adverse events occurred in 12.2%, and dose reductions were required in 21.5%. Patient-reported outcomes were not assessed in any of the studies. Conclusions: Our meta-analysis, encompassing both clinical trials and real-world data, confirms the encouraging efficacy of T-DXd in gastric/GEJ cancers, with a pooled ORR of 47.7% and a median PFS of 4.92 months, and supports its use as an early-line treatment in this challenging disease landscape. This analysis also highlights the significant incidence of grade ≥3 AEs, particularly neutropenia, which necessitates vigilant monitoring and proactive management. Future research should focus on optimizing patient selection, exploring combination therapies, and refining dosing strategies to maximize clinical benefit while mitigating toxicity.

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 <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 <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 <0.001), sepsis without shock (Risk difference: 0.016, 95% CI: 0.007 to 0.024, p-value <0.001), and sepsis with shock (Risk difference: 0.026, 95% CI: 0.018 to 0.034, p-value <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 < 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 <0.001), myocardial infarction (HR: 0.785, 95% CI: 0.769 to 0.801, p-value <0.001), ischemic stroke (HR: 0.665, 95% CI: 0.632 to 0.700, p-value <0.001), hemodialysis (HR: 0.445, 95% CI: 0.430 to 0.461, p-value <0.001) and sepsis (HR: 0.726, 95% CI: 0.714 to 0.738, p-value <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.

Abstract Introduction: BL and DLBCL are the two most common lymphomas associated with HIV infection. Notably, clinical trials often exclude HIV-positive patients and prior retrospective studies often lacked long-term follow-up on overall survival (OS). This has limited our knowledge about the influence of HIV status on survival in BL and DLBCL. Survival outcomes can also vary significantly across ethnic groups, influenced mostly by disparities in healthcare access and socioeconomic status. Additionally, survival rates differ among age groups, which may be attributed to tolerance to intensive chemotherapy and the presence of comorbid medical conditions. Our study primarily focused on comparing OS between HIV-positive and negative patients with DLBCL and BL in the real world. We also examined OS disparities among diverse ethnicities and age groups. Method: Patients diagnosed with DLBCL and BL were identified from the Cerner Health Facts database over five years from 2013 to 2018 using ICD-9 and ICD-10 codes. Within this cohort, individuals with a positive HIV status were identified through specific ICD-9 and ICD-10 codes. Demographic characteristics including age, gender, and ethnicity were collected for all patients, and they were stratified into distinct age groups: <20 years, 20-39 years, 40-59 years, 60-79 years, and 80+ years. OS was calculated for all patients from the time of diagnosis to time of death or hospice discharge. A multivariate cox regression model was employed to adjust for confounding variables. Results: The total number of patients diagnosed with DLBCL and BL was 10,534. Of these patients, 45.3% were female. The ethnic composition included 77% Caucasian, 10.3% African American and 12.7 % from other ethnicities. Among this population, 315 patients were HIV positive. In the cohort of DLBCL patients, 8,275 were HIV negative and 185 were HIV positive. In the cohort of BL patients, 1,944 were HIV negative and 130 were HIV positive. Among patients with DLBCL, HIV positive status had more than two-fold higher mortality rate compared to their HIV negative counterparts (HR=2.1, 95% CI 1.31 to 3.36, p=0.0018). Patients with BL who were HIV positive had no difference in OS in comparison to the HIV negative group (p=0.575). African American patients with DLBCL had almost 40% increased risk of mortality compared to Caucasian patients (HR=1.39, 95% CI 1.05-1.83, p=0.017). African American patients with BL had no difference in OS compared to Caucasian patients (p=0.3). Patients aged 60-79 years were found to have 44% higher risk of mortality compared to 40-59 age group (HR=1.44, 95% CI 1.13-1.83, p=0.0033) and patients aged 80 years or above were found to have more than two-fold higher risk of mortality in the DLBCL cohort (HR=2.16, 95% CI 1.63-2.87, p<0.0001). For patients with BL, those aged 20-39 had half the risk of mortality as compared to the 40-59 age group (HR= 0.50, 95% CI 0.28 - 0.87, p=0.014) whereas patients aged 80 or older had almost three times higher risk of mortality (HR = 2.87, 95% CI 1.81-4.57, p<0.0001). Conclusion: HIV status can significantly influence survival outcomes in patients diagnosed with DLBCL. Early identification of HIV infection, along with the initiation of prompt antiretroviral therapy and the administration of appropriate intensive chemotherapy regimens, is crucial for optimizing treatment outcomes in this patient population. Notably, our study indicates that African American patients exhibit a higher mortality rate compared to their Caucasian counterparts with DLBCL. This could be related to disparities in access to healthcare and treatment resources across different ethnicities. Moreover, it also indicates possible lymphoma biological heterogeneity in various ethnicities. Furthermore, elderly patients demonstrate increased mortality rates likely attributed to a greater prevalence of frailty, indicating the need for innovative less intense regimens for these patients with DLBCL and BL.

325 Background: Enhanced screening and detection along with novel chemotherapeutic regimens have improved survival among patients with breast cancer. Palliative care plays an important role in both pain management as well as addressing individualized goals of care. Newer treatment options are often implemented in patients with advanced breast cancer and have the potential to cause further treatment related adverse effects. We aim to understand the impact of an inpatient palliative care encounter on outcomes among patients with breast cancer. Methods: We utilized the 2020 National Inpatient Sample (NIS) Database in conducting a retrospective cohort study. We identified hospitalized patients who have breast cancer and subsequently had a palliative care encounter using appropriate ICD-10 CM codes. We stratified patients based on whether they had a palliative care encounter during the hospitalization or not. A survey multivariable logistic and linear regression analysis was used to calculate adjusted odds ratios (ORs) for the primary and secondary outcomes. A p value of < 0.05 was considered statistically significant. Results: We identified a total of 24770 hospitalized patients with breast cancer, of which 8.70% (2155/24770) had an in-patient palliative care encounter. The overall in-hospital mortality among those with breast cancer was 3.37% (835/24770). Among those who had a palliative care encounter, the overall in-hospital mortality rate was significantly higher at 25.75% (555/2155) (p = < 0.001). Utilizing a stepwise survey multivariable logistic regression model that adjusted for patient and hospital level confounders, the inpatient palliative care encounter among hospitalized patients with breast cancer significantly increased the risk for in-hospital mortality (adjusted OR 17.01, 95% confidence interval [CI], 11.11-26.04; p = < 0.001), longer hospital LOS (coefficient 2.63, CI 1.56-3.70; p = 0.001), and lower total hospital charges (coefficient -$14893; CI –[$24071 – $5714], p = 0.001). Conclusions: Our analysis revealed that an in-hospital palliative care encounter among patients with breast cancer was associated with a significantly lower cost of healthcare utilization. We also noted a significantly higher in-hospital mortality and longer length of hospitalization among this subgroup utilizing palliative care. Caution should be exercised in interpreting these results as they may reflect uncontrolled and more advanced disease in patients requiring an inpatient palliative care consultation. Further prospective studies are needed to better understand the financial impact on healthcare utilization as well as short and long-term outcomes in this patient population.

34 Background: Colorectal cancer is the third most common cancer worldwide. Newer treatment options have significantly improved quality of life in these patients, albeit with the potential for more adverse effects. Patients with colorectal cancer tend to have varying degrees of protein energy malnutrition (PEM) due to multiple reasons, including cancer-related cachexia, sarcopenia, and adverse effects of chemotherapy. Therefore, the impact of PEM on outcomes among patients with colorectal cancer needs further exploration. Methods: We utilized the 2020 National Inpatient Sample (NIS) Database in conducting this retrospective cohort study. We identified patients with colorectal cancer and PEM using appropriate ICD-10 diagnostic codes. We stratified patients with colorectal cancer based on the presence or absence of PEM. A survey multivariable logistic and linear regression analysis was used to calculate adjusted odds ratios (ORs) for the primary and secondary outcomes. A p value of < 0.05 was considered statistically significant. The aim of this study was to investigate the impact of PEM on in-hospital mortality, hospital length of stay (LOS), and total hospitalization charges among patients with colorectal cancer. Results: We identified a total of 77130 hospitalized patients with colorectal cancer, of which 11.06% (8535/77130) had comorbid PEM. The overall in-hospital mortality among patients with colorectal cancer was 2.74% (2115/77130). Among those with concomitant PEM, the mortality rate was significantly higher at 8.03% (686/8535, p < 0.001). Utilizing a stepwise survey multivariable logistic regression model that adjusted for patient and level confounders, PEM was found to be an independent predictor of increased in-hospital mortality (adjusted OR 2.94; 95% (confidence interval [CI] 2.26-3.81; p < 0.001), longer LOS (coefficient 5.37 days; CI 4.84-5.90; p < 0.001), higher total hospitalization charge ($53844; CI $45188-$62499; p < 0.001), increased need for mechanical ventilation (adjusted OR 3.87; CI 2.96-5.06; p < 0.001), and increased need for renal replacement therapy (adjusted OR 2.20; CI 1.08-4.50; p = 0.029). Conclusions: Our analysis demonstrated that PEM was widely prevalent in hospitalized patients with colorectal cancer and was associated with significantly higher in-hospital mortality and longer length of hospitalization. PEM was also associated with a significantly higher cost of healthcare utilization, increased need for mechanical ventilation and renal replacement therapy. A proactive approach to promote nutritional assessment and early nutritional optimization is indicated. Further prospective studies are needed to better understand the impact of nutritional optimization on the financial burden as well as short and long-term outcomes in this patient population.

7018 Background: CAR-T cell therapy represents a notable advancement in treating relapsed/refractory (R/R) hematological malignancies. Adverse events include CRS, infections, and neurological and cardiac complications. While there are reports from major academic institutions on the adverse effects of CAR-T therapy, we used data from the National Inpatient Sample (NIS) to gather national estimates of complications related to CAR-T therapy. Methods: A retrospective study was conducted to analyze patients who underwent CAR-T cell therapy by utilizing appropriate ICD-10-PCS procedure codes (XW033C3, XW043C3, XW23346, XW24346, XW23376, and XW24376) from NIS 2019 to 2021. Data regarding infections, toxic encephalopathy (a surrogate for neurological toxicity), and adverse cardiac events were extracted using relevant ICD-10-CM diagnostic codes. Patients experiencing various grades of CRS were identified through specific ICD-10 codes available in 2021 (Grades 1-5: D89.831-D89.835). Results: This study analyzed 6515 patients who underwent CAR-T cell therapy from January 2019 to December 2021. Among them, 60.7% were male. 74.6% were Caucasian, 11.7% were Asian and 6.7% were African American. 49.8% of patients had private insurance, 36.2% had Medicare, and 8.6% had Medicaid. 6.8% of patients were diagnosed with pneumonia, while sepsis occurred in 7.4% of patients and 3% experienced septic shock. 19.4% of patients experienced cardiac arrhythmias, and major cardiovascular events were recorded in 4.7% of the cohort. Acute myocardial infarction and stroke were documented in 0.6 and 1.2% of patients, respectively. Toxic encephalopathy was reported in 19.7% of patients. Among 2235 patients identified to have received CAR-T in 2021, 59.7% developed CRS. Grade 1 and grade 2 CRS were reported in 32% and 21% of patients, respectively, while grade 3 and grade 4 reactions were noted in 4.7% and 2% of patients, with no cases of grade 5 identified. The mean total cost of hospitalization was 308,364$, and the mean length of hospital stay was 19.5 days. The overall in-hospital mortality rate was 3.4%. Conclusions: Our study describes real-world outcomes from a large dataset of CAR-T patients. Infections pose a significant challenge with CAR-T therapy, highlighting the importance of early detection and timely antimicrobial treatment. CRS is common, with a 60% incidence, similar to previous clinical trials (55%). Immediate management is crucial for addressing CRS toxicity. Adverse neurological and cardiovascular incidents are often reported, emphasizing the need for meticulous monitoring and coordinating multidisciplinary care plans. The financial burdens also bear mentioning: CAR-T therapy costs significantly higher than autologous stem cell transplants. Further studies to address these issues are warranted.