Nimmagadda, Rithish

e23089 Background: Sodium–glucose cotransporter-2 (SGLT2) inhibitors are increasingly used for glycemic and cardiovascular benefits; however, concerns persist regarding genitourinary infections, particularly in vulnerable populations such as patients with cancer and diabetes. Real-world data evaluating the safety of SGLT2 inhibitors in this population remain limited. We evaluated the association between SGLT2 inhibitor use and genitourinary infection risk among cancer patients with type 2 diabetes. Methods: We conducted a retrospective cohort study using the TriNetX federated research network. Adult patients (≥18 years) with malignant neoplasms and type 2 diabetes mellitus were identified. Patients were stratified based on exposure to SGLT2 inhibitors and compared with cancer patients with diabetes not receiving SGLT2 inhibitors. Primary outcomes included urinary tract infection (UTI) and cystitis, identified using ICD-10 diagnostic codes. Analyses included unadjusted comparisons, 1:1 propensity score matching (PSM), and a Cox proportional hazards model as a sensitivity analysis to assess time to first UTI within one year following index exposure. Results: A total of 7,485 patients were included (7,137 without SGLT2 inhibitors and 348 with SGLT2 inhibitors). In unadjusted analyses, crude rates of UTI and cystitis were numerically higher in the SGLT2 inhibitor cohort. After 1:1 propensity score matching (312 patients per cohort), baseline characteristics were well balanced. The incidence of UTI was identical between matched cohorts (6.41% vs 6.41%, p = 1.00), with no significant differences observed for cystitis or acute cystitis. In a Cox proportional hazards sensitivity analysis, SGLT2 inhibitor use was associated with a significantly lower hazard of UTI compared with no SGLT2 inhibitor exposure (hazard ratio 0.68, 95% confidence interval 0.52–0.89; p = 0.0048). Conclusions: In this large real-world cohort of cancer patients with diabetes, SGLT2 inhibitor use was not associated with an increased risk of genitourinary infections. Propensity-matched analyses demonstrated no difference in absolute infection risk, while time-to-event analysis suggested a lower hazard of UTI among patients receiving SGLT2 inhibitors. These findings support the genitourinary safety of SGLT2 inhibitors in cancer patients with diabetes and may inform clinical decision-making in this high risk population.

e19562 Background: Multiple myeloma is a chronic blood cancer in which patients often live for many years, yet the risk of death remains ongoing. While survival has improved over time, population-level studies that combine traditional survival analysis, advanced modeling techniques, and future burden projections are limited. Methods: We performed a population-based retrospective study using the Surveillance, Epidemiology, and End Results (SEER) database. Overall survival was evaluated using Kaplan–Meier analysis and Cox proportional hazards regression. Parametric survival modeling was conducted using Weibull regression to better characterize long-term mortality patterns. Machine-learning survival analysis was performed using random survival forests to assess the relative importance of clinical and demographic factors. Annual case counts were analyzed and projected through 2035 using time-series forecasting methods. Results: The study included 8,627 patients with multiple myeloma. Overall survival declined gradually over long-term follow-up, with approximately one-quarter to one-third of patients surviving at extended time points. Female patients experienced better survival than males. Significant survival differences were observed across racial groups, with Asian or Pacific Islander patients demonstrating the most favorable outcomes and American Indian or Alaska Native patients the poorest. In multivariable analyses, age, sex, race, and year of diagnosis were independently associated with survival. Parametric modeling closely mirrored non-parametric survival estimates and supported a time-dependent pattern of mortality. Machine-learning analysis identified year of diagnosis as the strongest predictor of survival, followed by age and race. Forecasting suggested that the burden of multiple myeloma will remain substantial through 2035. Conclusions: Multiple myeloma is associated with long-term survival but persistent mortality risk and ongoing demographic disparities. Combining traditional survival analysis with parametric and machine-learning approaches provides a more complete understanding of outcomes and highlights the sustained future burden of this disease, with important implications for clinical care and healthcare planning.

e18542 Background: Outcomes in adult acute lymphocytic leukemia (ALL) remain heterogeneous and strongly influenced by age. However, population-level survival gradients across older age strata and the future burden of disease in an aging population remain incompletely characterized. We evaluated long-term survival patterns and projected disease burden in adult ALL using national registry data. Methods: We conducted a retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER) database including adults aged 50–89 years diagnosed with ALL between 2000 and 2022. Overall survival (OS) was estimated using Kaplan–Meier methods and compared across age and racial subgroups. Multivariable Cox proportional hazards regression was performed to identify independent predictors of mortality. Temporal trends in annual case counts were analyzed and projected through 2035 using time-series forecasting methods. Results: A total of 7,298 adult ALL patients were included. OS declined progressively with advancing age, demonstrating clear stepwise separation across age strata. Compared with patients aged 50–54 years, mortality risk increased incrementally across successive age groups, reaching more than fourfold higher risk among patients aged 85–89 years on multivariable analysis. Race-based survival differences were observed on unadjusted analysis; however, these differences were attenuated after adjustment for age and clinical factors. More recent year of diagnosis was independently associated with modest survival improvement, reflecting incremental therapeutic progress. Forecasting analysis projected a continued rise in adult ALL case burden through 2035, with widening uncertainty intervals over time, indicating sustained future healthcare impact. Conclusions: Adult ALL outcomes remain strongly age dependent, with sharply escalating mortality risk among older patients despite gradual therapeutic improvements. Projections indicate a sustained and growing disease burden in the United States. These findings highlight the urgent need for age-adapted treatment strategies, improved inclusion of older adults in clinical trials, and healthcare system preparedness to address the needs of an aging leukemia population.

e16469 Background: Pancreatic cancer remains among the most lethal malignancies worldwide, with limited improvement in survival despite therapeutic advances. Contemporary real-world data characterizing recent diagnosis acceleration, demographic disparities, and future burden remain limited. We evaluated national trends in pancreatic cancer burden using a large federated electronic health record (EHR) network. Methods: We conducted a retrospective multicenter real-world cohort analysis using the TriNetX Research Network. Adult patients (≥18 years) with pancreatic cancer were identified using ICD-10-CM code C25. Annual newly recorded diagnosis proportions, prevalence, and incidence rates were calculated for calendar years 2020–2024 and stratified by age, sex, race, and ethnicity. New diagnoses were defined as first recorded pancreatic cancer encounters within each calendar year. Exploratory future burden projections were generated through 2028 using autoregressive integrated moving average (ARIMA) time-series modeling. Results: Between 2020 and 2024, newly recorded pancreatic cancer diagnoses increased from 0.032% (21,118 cases) to 0.046% (23,660 cases), representing a descriptive relative increase exceeding 40%. Prevalence increased from 0.101% (65,971 cases) to 0.145% (74,139 cases), reflecting rapid expansion of disease burden. Diagnosis burden increased markedly with advancing age, with the highest burden observed among individuals aged ≥65 years. Males consistently demonstrated higher diagnosis proportions compared with females. Racial stratification demonstrated higher recorded diagnosis proportions among White and Asian populations, while substantial prevalence burden persisted across all racial groups, potentially reflecting differences in healthcare utilization and access. Non-Hispanic individuals exhibited higher diagnosis and prevalence proportions compared with Hispanic individuals. Exploratory ARIMA forecasting projected continued growth in pancreatic cancer burden through 2028, with widening uncertainty intervals over time, indicating escalating long-term healthcare demand. Conclusions: Pancreatic cancer burden in the United States is rapidly increasing, with disproportionate impact among older adults and males and persistent demographic disparities. Exploratory projection modeling suggests continued expansion of disease burden in the near term. These findings highlight the urgent need for earlier detection initiatives, risk-adapted screening strategies, and healthcare system preparedness to address the growing national impact of pancreatic cancer.

e16322 Background: Small intestine neuroendocrine carcinoma (NEC) is a rare, aggressive malignancy comprising less than 0.1% of gastrointestinal cancers. Population-level data remain limited, restricting understanding of long-term survival patterns, demographic disparities, and evolving disease burden. We evaluated survival outcomes, demographic predictors, and incidence trends of small intestine NEC in the United States. Methods: We conducted a retrospective population-based cohort study using SEER Research Data (17 registries, November 2024 submission). Patients diagnosed with malignant small intestine NEC (ICD-O-3 morphology code 9.3.3.1.2) between 2000 and 2022 were identified using SEER*Stat (v9.0.4.2). Variables including age group, sex, race, year of diagnosis, survival time, and vital status were analyzed in R (v4.5.1). Overall survival (OS) was estimated using Kaplan–Meier methods and compared using log-rank testing. Cox proportional hazards models identified independent predictors of OS. Annual case counts were modeled using time-series forecasting to project future incidence. Results: A total of 506 patients were included. Estimated OS was 94.4% (95% CI 92.4–96.4) at 1 year, 88.1% (85.3–91.0) at 3 years, and 82.4% (79.0–85.9) at 5 years, with a subset demonstrating survival beyond 15 years. Increasing age was associated with worse survival (log-rank p = 0.058). Significant racial differences in OS were observed (log-rank p < 0.0001). In multivariable analysis, race remained independently associated with OS. Incidence forecasting projected a modest increase in annual case burden over the next decade. Conclusions: Small intestine NEC demonstrates heterogeneous survival outcomes, significant demographic disparities, and projected growth in disease burden. These findings highlight the need for improved risk stratification, equitable access to care, and integration of molecular and treatment-level data to optimize management of this rare malignancy

e15598 Background: Immune checkpoint inhibitors (ICIs) have transformed the treatment landscape of gastrointestinal (GI) malignancies. Emerging evidence suggests that gut microbiome composition plays a critical role in modulating the efficacy of immunotherapy. Antibiotics, by disrupting intestinal microbial diversity, may attenuate antitumor immune responses and compromise ICI outcomes. We evaluated time-dependent clinical outcomes associated with antibiotic exposure using real-world data. Methods: We conducted a retrospective cohort study using a large federated real-world database (2015-2025). Adults (18–89 years) with gastrointestinal or hepatobiliary malignancies (including colorectal, gastric, esophageal, and liver cancers) treated with ICI, receiving systemic antibiotics, were compared with matched controls without antibiotic exposure. Cohorts were balanced using 1:1 Propensity score matching for demographics, comorbidities, and treatment variables. The primary outcome was all-cause mortality at 30 days of ICI initiation; the secondary outcomes were hospitalization secondary to infectious and organ-related complications, overall survival at 1 and 3 years. Pre-specified subgroup analyses were performed in older adults ( > / = 65 years). Effect estimates were reported as risk ratios( RR), hazard ratios (HR), and absolute risk differences. Survival was analyzed using Kaplan–Meier curves and Cox proportional hazards models. Results: Within 30 days, antibiotic exposure was associated with significantly increased risks of Clostridioides difficile infection (RR 2.39), pneumonia (RR 2.93), acute kidney injury (RR 1.40), acute respiratory failure (RR 2.11), and neutropenia (RR 1.18) (all p < 0.05). Absolute risk differences translated to a number needed to harm (NNH) of approximately 38 for pneumonia, 143 for acute kidney injury, and ~140 for C. difficile infection. One-month mortality was modestly higher in the antibiotic group (5.4% vs 4.5%; HR 1.22; p = 0.014). However, no significant differences in mortality were observed at 6 months, 1 year, or 3 years, and survival curves converged over time. In the subgroup analysis of adults ≥65 years, early adverse event patterns were preserved, while long-term mortality remained unchanged. One-year hospital admission rates did not differ significantly between groups. Conclusions: Antibiotic exposure is associated with substantial early infectious and organ-related harm and a small increase in short-term mortality, without improvement in long-term survival, including among older adults. These findings highlight a critical opportunity for risk-adapted antibiotic stewardship and careful reassessment of empiric antibiotic use. Key words: ICI- Immune checkpoint inhibitors, RR- Risk ratio, HR- Hazard Ratio, NNH- Number Needed to Harm.

8075 Background: The role of definitive local thoracic therapy in metastatic non–small cell lung cancer (NSCLC) remains controversial. While stereotactic body radiation therapy (SBRT) is increasingly utilized, comparative survival outcomes with surgical resection in real-world populations remain limited. We evaluated survival and pulmonary outcomes associated with surgery versus SBRT in patients with stage IV NSCLC. Methods: We conducted a retrospective cohort study using the TriNetX Research Network including adults (≥18 years) with stage IV NSCLC treated between January 2013 and December 2023 who underwent definitive local thoracic therapy with either surgical resection or SBRT. Patients with small cell lung cancer, prior lung cancer diagnoses, prior thoracic radiation, or incomplete survival data were excluded. Propensity score matching (1:1) was performed to balance demographics, comorbidities, smoking history, and exposure to systemic therapy including chemotherapy and immunotherapy within 6 months of index treatment. Primary outcomes included landmark 1-year all-cause mortality and overall survival. Secondary outcomes included pneumonia and respiratory failure. Kaplan–Meier analysis and Cox proportional hazards regression were performed. Results: After matching, 1,934 patients were included (967 per cohort). At 1 year, surgical resection was associated with significantly lower mortality compared with SBRT (17.5% vs 31.4%; RR 0.56, 95% CI 0.47–0.66; p < 0.001), corresponding to an absolute risk reduction of 13.9% and an estimated number needed to treat of approximately 7. Kaplan–Meier analysis demonstrated superior survival in the surgical cohort (log-rank p < 0.001). Surgical resection remained associated with significantly improved long-term survival, with a 64% lower hazard of death (HR 0.36, 95% CI 0.30–0.44; p < 0.001) and prolonged median survival (3,942 vs 1,182 days). Pulmonary outcomes favored surgery. Pneumonia incidence was significantly lower in the surgical cohort at both 1 year (12.9% vs 29.3%; RR 0.44; p < 0.001) and 3 years (5.9% vs 14.2%; RR 0.42; p < 0.001). Rates of respiratory failure did not differ significantly between treatment groups. Conclusions: In this large real-world propensity-matched study, surgical resection was associated with significantly improved survival compared with SBRT in carefully selected patients with stage IV NSCLC. Surgery was additionally associated with lower long-term pulmonary infectious complications without increased respiratory failure risk. These findings suggest a potential role for aggressive local therapy in selected metastatic patients and support prospective trials to refine patient selection strategies.

3605 Background: Metabolic status and systemic inflammation are increasingly recognized as important modifiers of immune checkpoint inhibitor (ICI) response. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) exhibit anti-inflammatory and immunomodulatory properties and are widely used in diabetes and obesity. However, their clinical impact on immunotherapy outcomes in metastatic colorectal cancer (mCRC) remains unclear. Methods: We conducted a retrospective observational cohort study using the TriNetX Global Collaborative Network, including electronic health records from 170 healthcare organizations between 2015 and 2025. Adults with mCRC who received at least one ICI were identified. Patients prescribed GLP-1 RAs within six months before or after ICI initiation were compared with non-exposed controls. Patients with prior bariatric surgery were excluded. Cohorts were balanced using 1:1 propensity score matching for demographics, metabolic conditions, and major comorbidities. Primary endpoint was all-cause mortality at 1, 3, and 5 years. Secondary outcomes included pneumonia, heart failure exacerbation, and major abdominal surgical procedures. Survival analyses were performed using Kaplan–Meier methods and Cox proportional hazards models. Results: Among 8,304 eligible patients, 148 received GLP-1 RAs. After propensity matching, 138 patients were included in each cohort with well-balanced baseline characteristics. At 1 year, mortality was lower in the GLP-1 cohort (27.5% vs 40.6%), corresponding to a 32% relative risk reduction (RR 0.68, 95% CI 0.49–0.95) and reduced hazard of death (HR 0.67, 95% CI 0.43–1.03). This association persisted at 3 years (27.5% vs 41.3%; RR 0.67, 95% CI 0.48–0.93; HR 0.68, 95% CI 0.45–1.05) and 5 years (28.3% vs 42.0%; RR 0.67, 95% CI 0.49–0.93), with higher 5-year survival probability (50.5% vs 41.5%). Secondary outcomes favored GLP-1 exposure, including lower incidence of pneumonia (10.9% vs 17.4%; HR 0.58) and fewer heart failure exacerbations (23.9% vs 31.9%; HR 0.75). Rates of major abdominal surgical procedures were numerically lower in the GLP-1 cohort. Conclusions: In this large real-world cohort, concurrent GLP-1 RA exposure was associated with clinically meaningful and durable survival benefit in mCRC patients receiving ICIs, without increased adverse clinical outcomes. These findings suggest a potential immunometabolic interaction and support prospective evaluation of GLP-1–based strategies as adjunctive modifiers of immunotherapy response.

11186 Background: Cancer survival is shaped by tumor biology, treatment access, and socioeconomic context, yet population-level quantification of long-term survival disparities related to chemotherapy use and income is limited. We assessed five-year cancer-specific survival across demographic, treatment, and socioeconomic strata in a national registry. Methods: We performed a retrospective, population-based survival analysis using the Surveillance, Epidemiology, and End Results (SEER) database. Cancer-specific survival was evaluated at 12, 24, 36, 48, and 60 months after diagnosis. Outcomes were stratified by sex, race, chemotherapy receipt, and area-level median household income categories. Survival estimates were summarized descriptively and visualized using time-to-event curves. Results: Overall cancer-specific survival declined progressively over five years, from ~84% at 12 months to ~58% at 60 months. Sex differences were minimal, with similar five-year survival among males and females (~57–58%). Racial disparities were substantial: Asian/Pacific Islander patients demonstrated the highest survival across follow-up, while Black and American Indian/Alaska Native patients had lower early survival and persistent gaps at five years. Patients with recorded chemotherapy use had improved survival compared with those without or with unknown chemotherapy status; 12-month survival was ~88% versus ~80%, and five-year survival was ~65% versus ~57%, respectively. A pronounced socioeconomic gradient was observed: individuals in areas with median household income ≥$120,000 had higher five-year survival (~67%), whereas those in areas with income < $40,000 had markedly lower survival (~52%). Conclusions: In this national registry analysis, both chemotherapy utilization and higher socioeconomic status were strongly associated with improved long-term cancer survival, whereas persistent racial and income-related disparities remained evident. These findings highlight ongoing inequities in access to oncologic care and support the need for targeted policy interventions and equity-focused treatment delivery models. Interpretation should account for limitations inherent to observational registry data and potential residual confounding.

Abstract Background: Hematologic toxicity, including early and prolonged neutropenia, anemia, and thrombocytopenia, is among the most common and clinically significant complications after CD19, CD20, CD22 and BCMA-directed CAR-T therapy. Several clinical scoresmost notably CAR-HEMATOTOX (CAR-HT) and the refined ALL-HThave been developed to predict post-infusion cytopenias, but their comparative performance across diseases has not been systematically evaluated. No prior review has summarized existing models or assessed the need for AI-based predictive approaches. Methods: We conducted a systematic review of studies that developed or validated predictive models or risk scores for hematologic toxicity after CAR-T therapy in hematologic malignancies. Eligible studies included clinical, cytokine-based, or composite predictors and reported discrimination metrics such as area under the curve (AUC). Extracted variables included CAR-T product, target antigen, disease type, predictors used, model type, validation strategy, and performance statistics. Results were synthesized qualitatively due to heterogeneity in model structure and outcome definitions. Results: Studies on the CAR-HT score in B-cell lymphomas and multiple myelomas reported AUC values of 0.89 and 0.82, respectively, for predicting severe or long-term neutropenia after CD19 and BCMA-directed CAR-T therapy. Studies on the ALL-HT score (a modified/refined version of CAR-HT replacing ferritin with bone-marrow burden to improve discrimination in B-ALL) reported AUC 0.84-0.90 for predicting prolonged neutropenia and worse overall survivability (OS) after CD19/CD22 CAR-T. A multicenter study including aggressive/indolent NHL, MM/PCL, and ALL patients treated with CD19, CD20, or BCMA CAR-T reported AUC 0.87 (eIPM-Pre) and 0.88 (eIPM-Post) for predicting ICA-HT. A CD19 CAR-T study in B-ALL and LBCL reported AUC 0.85 for an early hematotoxicity nomogram using TNF- and CRP. Conclusion: Existing prediction tools for hematologic toxicity after CAR-T therapy demonstrate strong but disease-specific performance. Yet inconsistent endpoints and heterogeneous predictors limit clinical generalizability. No current model incorporates contemporary AI or machine-learning methods, underscoring a significant unmet need. Advanced predictive frameworks may allow earlier identification of patients at risk for severe or prolonged cytopenias and guide more individualized supportive care, with the potential to reduce downstream complications. Citation Format: Mansha Gupta, Abhijith Vemulapalli, Swathi Cherukuri, Rithish Nimmagadda, Akhil Jain. Predictive models for hematologic toxicity after CAR-T therapy: A systematic review of current risk scores and unmet AI needs [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 5202.