Citations

Abstract Introduction: CAR T-cell therapy is an important treatment option for patients with relapsed or refractory (R/R) DLBCL. Three CAR T-cell products have received approval: axicabtagene ciloleucel (Yescarta), lisocabtagene maraleucel (Breyanzi), and tisagenlecleucel (Kymriah). Although direct head-to-head studies comparing the three therapies do not exist, clinical trials have revealed notable differences in response rates and remission rates among them. All three products induce CRS and ICANS; however, variations in the incidence and severity of these adverse effects have been observed. We utilized data from the National Inpatient Sample (NIS) to gain further insights into the incidence of various adverse events associated with different CAR-T products in DLBCL. Method: In this retrospective study, the 2022 NIS database was used to identify hospitalizations with DLBCL and those who received Yescarta, Breyanzi, or Kymriah using appropriate ICD-10-CM diagnostic and ICD-10-PCS procedure codes. Data on CRS, ICANS, infections, and adverse cardiac events were extracted using relevant ICD-10-CM codes. These outcomes were compared across different CAR-T products using Pearson's chi-square analysis. Multivariate logistic regression was also performed, adjusting for demographics, hospital-specific characteristics, and comorbidities. Results: We identified 1440 patients with DLBCL. Among these, 1100 patients (64.6% male; 70.7% Caucasian, 8.8% African American, 20.5% other ethnicities) received Yescarta, 90 patients (66.7% male; 82.4% Caucasian, 0% African American, 17.7% other ethnicities) received Kymriah and 250 patients (64% male; 82.6% Caucasian, 10.9% African American, 6.5% other ethnicities) received Breyanzi. The incidence of CRS was 52% for Breyanzi, 44.4% for Kymriah and 68.6% for Yescarta, and the difference was statistically significant by chi-square analysis (p = 0.03). This difference remained statistically significant for Kymriah after multivariate analysis [Adjusted Odds ratio (OR) = 0.3, CI 0.1 to 0.9, p=0.032], but not for Breyanzi (Adjusted OR = 0.3, CI 0.1 to 0.9, p=0.032) in comparison to Yescarta. The incidence of ICANS was 16% for Breyanzi, 22.2% for Kymriah, and 33.2% for Yescarta, with a statistically significant difference observed by chi-square analysis (p = 0.05). This difference remained statistically significant for Breyanzi after multivariate analysis [Adjusted OR = 0.3, CI 0.1 to 0.6, p=0.002], but not for Kymriah (Adjusted OR = 0.6, CI 0.1 to 2.9, p=0.551) in comparison to Yescarta. Among cardiovascular events, there was no significant difference in the incidence of acute myocardial infarction (Yescarta vs Kymriah vs Breyanzi, 0.5% vs 0% vs 0.2%, p = 0.487), stroke (0.5% vs 5.6% vs 2%, p = 0.07), cardiogenic shock (0.5% vs 0% vs 0%, p = 0.880), and arrhythmias (20.9% vs 27.8% vs 32%, p = 0.258) among these CAR T-cell therapies. Furthermore, there were no significant differences in the incidence of infectious complications, including pneumonia (5.9% vs 5.6% vs 2%, p = 0.510), sepsis (5% vs 5.6% vs 6%, p = 0.962), or septic shock (2.3% vs 0% vs 0%, p = 0.535) among these CAR T-cell therapies. There was no difference in all-cause in-hospital mortality across these therapies (2.3% vs 5.6% vs 2%, p = 0.692). Conclusion: Kymriah showed lower CRS rates and Breyanzi showed lower ICANS rates in comparison to Yescarta in our study. All CAR T-cell therapies have the potential to cause infections and cardiac events, which require monitoring, early identification and prompt treatment. When selecting among various CAR T-cell products, several factors must be considered, including the patient's lymphoma type, prior treatment history, manufacturing turnaround time, cost, availability, and potential short-term and long-term side effects. The limitations of our study include its retrospective nature, reliance on ICD-10 codes to identify patients with adverse events, and the absence of longitudinal data on long-term adverse events. Nevertheless, this study provides essential insights for hematologists regarding the incidence of specific adverse events associated with different CAR T-cell products within the real-world population.

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.

Abstract Background: Clostridioidesdifficile infection (CDI) represents a significant infectious complication in both Chimeric Antigen Receptor(CAR) T-cell therapy and hematopoietic stem cell transplant (HSCT) recipients. We sought to investigate the incidence and outcomesof CDI among various CAR-T therapy products. Methods: This retrospective study used the 2022 National Inpatient Sample Database to identify and include adult patients with a primary diagnosis of four hematologic malignancies (Non-Hodgkin Lymphoma (NHL), Multiple Myeloma (MM), Acute Lymphoblastic Leukemia (ALL), and Acute Myeloid Leukemia (AML). In this cohort, we isolated patients who developed CDI using ICD-10 codes. Subgroup analysis was performed based on the type of CAR-T cell therapy and HSCT recipients. Multivariate regression analysis was performed to identify independent risk factors for CDI and mortality. A p-value < 0.05 was considered statistically significant. Results: A total of 8,739 patients with CDI were identified among 507,559 patients with four hematologic malignancies, representing an overall incidence of 1.72%. Patients receiving CAR-T cell therapy (5% vs 2%, p<0.05), bone marrow transplant (BMT, 3% vs 2%, p<0.05), and those with a history of BMT (6% vs 2%, p<0.05) were at significantly higher risk for CDI. Among individual CAR-T products, the incidence was: for CD19-directed CAR-T, Brexu-cel 5%, Axi-cel 6%, Tisa-cel 5%, and Liso-cel 3%; for BCMA-directed CAR-T, Ide-cel 4% and Cilta-cel 5%. There was no significant difference in CDI rates between these individual CAR-T products. Among CAR-T recipients by cancer type, CDI incidence was NHL 5%, MM 4%, ALL 7%, and AML 5% (p=0.79). Multivariate regression identified history of HSCT (OR 2.11, 95% CI 1.09–4.08), cytokine release syndrome (OR 1.7; 1.26–2.52), protein-energy malnutrition (OR 2.08; 1.83–2.36), graft versus host disease (OR 2.52; 2.02–3.15), and female sex (OR 1.23; 1.10–1.38) as significant independent risk factors for CDI (all p<0.05). Overall mortality in those with CDI was 6% compared to 5% without, and mortality increased substantially to 36% in those requiring surgical intervention for CDI. Conclusion: In patients with hematologic malignancies, identifying risk factors and rates of CDI in CAR-T cell therapy is essential for prompt recognition and effective management. Future research on optimizing CDI screening protocol and prevention strategies can help reduce mortality and morbidity in this immunocompromised population.

Abstract Introduction Despite significant advancements in therapeutic strategies, acute lymphoblastic leukemia (ALL) continues to present a challenge with variable survival outcomes across diverse patient populations. It is increasingly evident that factors beyond clinical variables such as age, sex, race, income, and geographic location, play a critical role in determining prognosis. This study evaluates the impact of these factors on overall survival (OS) in patients with ALL using the SEER dataset. Methods Data were extracted from the SEER database (2002–2022) for patients diagnosed with ALL. Cases with incomplete survival data or missing key demographic variables were excluded. Variables included in the analysis were age, sex, race, household income (low <$50,000, mid $50,000–$74,999, and high ≥$75,000 income tiers), and geographic location. We used Kaplan-Meier survival curves to estimate the median survival time and multivariable Cox proportional hazards model to identify independent predictors of mortality. Result A total of 4,943 patients met inclusion criteria. The cohort was 56.6% male and 43.4% female. The majority of patients were White (77.3%), followed by Asian or Pacific Islander (11.9%), Black (7.4%), American Indian/Alaska Native (2.3%), and Unknown (1.1%). Most patients were aged 10–19 years (27.4%), 60–69 (12.9%), 50–59 (12.7%), with 11.9% aged 20–29 years. The median overall survival (OS) was 67 months. On Kaplan-Meier analysis, OS declined with age, from 43.0 months (95% CI: 33.0–56.0) in patients aged 40–49 to 2.0 months (95% CI: 2.0–3.0) in those ≥80. Median OS was 80.0 months (95% CI: 64.0–112.0) in males vs 58.0 months (95% CI: 49.0–79.0) in females. Patients in high-income areas had a median OS of 76.0 months (95% CI: 65.0–100.0) compared to 48.0 months (95% CI: 36.0–81.0) in mid-income areas. Among racial groups, Black patients had the shortest OS (33.0 months, 95% CI: 27.0–49.0), though race was not significant in adjusted models. On multivariable Cox regression, older age remained the strongest predictor of mortality. HR 1.54 (95% CI: 1.28–1.84) for age 40–49 and HR 7.90 (95% CI: 6.60–9.45) for age ≥80 (p < 0.001 for all). Male sex (HR: 1.10; 95% CI: 1.02–1.20; p = 0.018) and low income (HR: 1.29; 95% CI: 0.90–1.84; p = 0.165) were associated with worse outcomes, while high income was associated with better outcomes (HR: 0.90; 95% CI: 0.82–1.00; p = 0.045). Race and metropolitan residence were not independently associated with OS in the adjusted model.Conclusion In this population-based analysis of patients with ALL, older age, male sex, and lower income were independently associated with worse overall survival. While descriptive differences in survival were observed by race and geographic region, these factors were not statistically significant after adjustment. The findings highlight the critical role of age and socioeconomic status as determinants of ALL outcomes and underscore the need for targeted interventions to address these persistent disparities in care.

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.

Importance The prognosis of advanced pancreaticobiliary tumors is poor. Next-generation sequencing (NGS) of tissue samples is utilized to identify actionable alterations, but there are occasional limitations due to inadequate tissue acquisition. Circulating tumor DNA (ctDNA) is an alternative method, but its correlation with tissue-based NGS remains unexplored. Objectives To assess the mutation concordance (mCR) rates between ctDNA and tissue testing for patients with pancreatic ductal adenocarcinoma (PDAC) and cholangiocarcinoma (CC) and to evaluate how ctDNA performs as a treatment response biomarker. Design, Setting, and Participants This retrospective cohort study was conducted among patients with PDAC and CC treated at academic institutions from January 2014 to January 2025. Patients underwent ctDNA testing using 1 platform and tissue NGS testing using 2 platforms. Main Outcomes and Measures mCR, which measures the shared gene alterations observed by both ctDNA and tissue-based NGS testing, was calculated using the Spearman correlation for PDAC and CC. The performance of ctDNA as a treatment response biomarker was assessed by comparing serial ctDNA data with restaging scans and cancer antigen 19-9 levels in patients with PDAC. Results Our cohort included 790 patients: 570 with advanced PDAC (265 [46.5%] female; median [IQR] age, 64 [33-84] years) and 220 with advanced CC (95 [43.2%] female; median [IQR] age, 66 [42-88] years). Overall, 461 patients with PDAC (80.9%) and 192 patients with CC (87.2%) underwent ctDNA testing, while 239 patients with PDAC (41.9%) and 70 patients with CC (31.8%) had tissue NGS testing. Among patients with PDAC, 85 of 130 patients (65.4%) showed shared specific gene alterations between ctDNA and tissue testing; there was a significant mCR, with a Spearman correlation of 0.47 (95% CI, 0.28-0.62; P &amp;lt; .001). For patients with CC, 32 of 48 (66.7%) had shared alterations between ctDNA and tissue testing; there was a significant mCR, with a Spearman correlation of 0.56 (95% CI, 0.35-0.70; P &amp;lt; .001). A subgroup analysis of patients with PDAC who underwent serial ctDNA testing suggested that new TP53 subclones and increased ctDNA variant allele frequency levels of TP53 and KRAS were associated with higher odds of progressive disease (eg, increased TP53 frequency: odds ratio, 7.28; 95% CI, 2.15-24.66; P = .001). Conclusions and Relevance In this cohort study of patients with pancreaticobiliary tumors, there was a significant mCR between ctDNA and tissue NGS testing. Additionally, results suggest that ctDNA might detect resistant clones and enable assessment of treatment response.

4166 Background: GN is a front-line therapy for aPDAC. A Phase I/II study demonstrated that GCN has a higher overall response rate and median overall survival (mOS). Our previous study found no difference in outcomes among patients with DNA damage repair gene mutations; however, stromal gene expression correlated with mOS in patients receiving GCN. Here, we further evaluate differences in the outcomes with GCN and GN by site of biopsy. Methods: PDAC samples (n = 4,463) were analyzed by NGS (NextSeq/NovaSeq) or RNA (NovaSeq) (Caris Life Sciences, Phx, AZ). Expression of stromal and related genes ( ACTA2, ADIRF, HAS2, IL-6, MMP-2, MMP-9, SPARC, STAT3, TBGB1, TGFB2, TGFBR3, IDO1, HLA-DRB4, VEGFB) from different biopsy sites [high expression (H) >50% of RNA transcripts per million] was correlated with outcomes to GCN or GN. mOS was obtained from insurance claims and calculated from first treatment to last contact. The hazard ratio (HR) was calculated by the Cox proportional hazards model, and p-values were calculated using the log-rank test. Results: 4325 patients [primary biopsy (PT), n = 1,878; non-liver metastatic biopsy (N-LM), n = 818; Liver biopsy (LM), n = 1,629] received GN while 138 patients (PT, n = 45; N-LM, n = 28; LM, n = 65) received GCN. GCN was associated with longer mOS than GN [∆: 5.2 months (m), HR: 0.76, 95% CI 0.63-0.92, p = 0.01]. GCN was associated with longer mOS compared to GN in LM (∆: 5.6 m, HR: 0.66, 95% CI 0.50-0.87, p = 0.003), but it was not significant in PT (∆: 4.6 m, p = 0.13) and N-LM (∆: 4.4 m, p = 0.35). Median MMP2 (38.5 vs. 163.1 vs. 162.2), VEGFB (14.4 vs. 16.9 vs. 16.2) and TGFBR3 (11.4 vs. 15 vs. 16.4) expression were lower in LM compared to PT and N-LM while TGFB1 (41.6 vs. 34.5 vs. 39.8) and IL6 (1.61 vs. 1.19 vs. 1.41) expression were highest in LM (p < 0.05). In LM, IL6 -H (∆: -11 m, p = 0.037) and TGFB1 -H (∆: -5.9 m, p = 0.10) were associated with worse post-GCN survival compared to GN (p = 0.82 and p = 0.57). Whereas, in N-LM, TGFBR3 -H trended towards longer post-GCN survival (∆: 12 m, p = 0.18), while ADIRF -H trended towards shorter post-GCN survival (∆: -12 m, p = 0.056) compared to GN (p = 0.42 and p = 0.10). While in PT, MMP2 -H (∆: 11.3m, HR: 0.46, p = 0.16), TGFB1 -H (∆: 11.3 m, HR: 0.33, p = 0.09), HLA-DRB4 -H (∆: 12.9 m, HR: 0.44, p = 0.11) and VEGFB -H (∆: 10.7, HR: 0.34, p = 0.09) trended towards longer post-GCN survival compared to GN ( MMP2 -H, ∆: 3.4 m, p = 0.03, TGFB1 -H, p = 0.661, HLA-DRB4 -H, p = 0.67, VEGFB-H , ∆: 1.3 m, p = 0.03). Conclusions: GCN is associated with improved mOS compared to GN, especially in LM.Stromal gene expression in the liver differs from that in N-LM and the pancreas. While high stromal gene expression trends towards worse post-GCN survival in LM, it is associated with improved survival in N-LM and PT. Further validation is needed to understand the impact of stromal gene expression in different tumor sites on survival outcomes and signature development.

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.