Citations

e22593 Background: Pheochromocytoma is a rare neuroendocrine tumor, and population-level data describing long-term temporal trends are limited. Evaluating national patterns over time may improve epidemiologic understanding and clinical awareness. Methods: We performed a retrospective analysis of pheochromocytoma cases recorded in the Surveillance, Epidemiology, and End Results (SEER) database from 1975 through 2022. Annual case counts were examined overall and by race (White, Black, Other, and Unknown). Temporal trends were assessed using Poisson regression, and annual percent change (APC) was calculated to quantify changes over time. Results: A total of 408 pheochromocytoma cases were identified during the study period. Overall case counts increased significantly over time, with Poisson regression demonstrating a consistent upward trend corresponding to an APC of 5.8% per year (p < 0.001). White individuals accounted for the majority of reported cases, while Black and other racial groups had significantly lower case counts compared with the reference population. Visual assessment of decade-level trends suggested a gradual increase from 1975 through approximately 2010, followed by a sharper rise in more recent years. Conclusions: Pheochromocytoma case counts in the United States have increased substantially over the past five decades based on SEER data. These findings suggest evolving epidemiologic patterns in this rare tumor and emphasize the importance of continued surveillance. Observed trends should be interpreted in the context of potential changes in diagnostic practices, imaging utilization, and cancer registry reporting over time.

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.

e19559 Background: Timely initiation of systemic therapy is critical in multiple myeloma (MM), yet real-world variation in time to treatment initiation (TTI) and its association with clinical outcomes, treatment-related toxicities, and supportive care utilization remain incompletely characterized. Methods: We conducted a retrospective cohort study using the Epic Cosmos database (2015–2025). Adults with MM were identified using ICD-10-CM code C90. TTI was defined as days from MM diagnosis to first exposure to systemic anti-myeloma therapy, including proteasome inhibitors, immunomodulatory drugs, or anti-CD38 monoclonal antibodies. Patients were stratified into TTI < 30 days (n = 90015), 30–60(n = 81190), and > 60 days(119,245). Primary outcomes included mortality, infection (sepsis or pneumonia), AKI within 30 days, DVT/PE, and bone marrow transplant (BMT). Secondary outcomes included hemodialysis initiation, febrile neutropenia, thrombocytopenia, herpes zoster reactivation, and use of bone-protective therapy (zoledronic acid, pamidronate, or denosumab) and antiviral prophylaxis (acyclovir/valacyclovir). Outcomes are presented as unadjusted percentages with 95% confidence intervals. Results: Mortality demonstrated a U-shaped association with TTI, occurring in 22.99%, 21.32%, and 21.32% of patients in the < 30-day, 30–60-day, and > 60-day cohorts, respectively. Infection rates were 16.42%, 17.11%, and 17.30%, while AKI < 30 occurred in 16.01%, 16.38%, and 16.49%. BMT utilization was highest in the 30–60-day cohort (19.14%) compared with < 30 days (18.28%) and > 60 days (18.21%). VTE rates increased modestly with delayed treatment (9.39%, 9.82%, and 10.10%). HD occurred in 3.15%, 3.08%, and 3.07% of patients. Febrile neutropenia occurred in 17.15%, 18.03%, and 17.55%, thrombocytopenia in 13.34%, 13.93%, and 13.86%, and herpes zoster reactivation in 1.21%, 1.29%, and 1.42%. Antiviral prophylaxis use was highest in the 30–60-day cohort (91.25%) compared with < 30 days (88.48%) and > 60 days (88.23%). Bone-protective therapy use was also highest in the 30–60-day cohort (31.68%) versus < 30 days (28.90%) and > 60 days (23.79%). Conclusions: In this large real-world analysis, initiation of systemic therapy within 30–60 days of MM diagnosis was associated with lower mortality, higher transplant utilization, and greater use of guideline-recommended supportive care compared with both earlier and delayed treatment initiation. Patients treated within 30 days appeared to represent a higher-acuity phenotype, while delays beyond 60 days were associated with lower supportive care uptake and higher thrombotic risk. These findings suggest that time to treatment initiation may reflect both disease severity and care delivery quality, and identify a potentially actionable window to optimize treatment pathways and supportive care in multiple myeloma.

e19094 Background: WM/LPL is an indolent B-cell Non-Hodgkin Lymphoma with prolonged survival and predisposition to secondary malignancies (SM) influencing clinical outcomes and survivorship care. We evaluated the incidence, demography, treatment utilization, and outcomes of SM in patients with WM/LPL using population-based data. Methods: SEER-22 database was used to identify patients with LPL/WM diagnosed between 2000–2022 and stratified by SM. Overall survival (OS) was analyzed using Kaplan–Meier survival analysis and propensity score matched Cox regression was used to assess mortality risk. Hazard ratios were reported, with p<0.05 deemed significant. Results: 22,170 patients with WM/LPL were identified, with a median age of 71 years (IQR 16); the cohort was predominantly male (59.0%), White (84.0%), had a median household income of $50,000–$75,000 (48.9%), and resided primarily in urban areas (89.5%). Among all WM/LPL patients, 20.8% (n=4,615) developed a SM. Patients who developed SM were older than those without (median age 75 vs 70 years, p<0.0001) with 45.2% alive at predefined follow-up. The most common solid organ SM were gastrointestinal adenocarcinoma (16%), prostate cancer (14%), and lung adenocarcinoma (9%), while the leading hematologic SM were plasma cell myeloma (6%), diffuse large B-cell lymphoma (5%), and myelodysplastic syndrome (2%). 35.3% of the cohort received chemotherapy, while 0.1% received cancer-related surgery or radiation. On multivariable analysis, older age (OR 0.82, 95% CI 0.81–0.83), male sex (OR 0.59, 95% CI 0.44–0.80), urban residence (OR 1.99, 95% CI 1.24–3.18), and higher income (OR 2.16, 95% CI 1.13–4.15) were significantly associated with SM diagnosis. Kaplan–Meier analysis demonstrated inferior survival among patients with SM (54.8% vs 45.2%, p<0.0001), with shorter median OS (9 vs 14 years, log-rank p<0.001). Similarly, Propensity-matched analysis revealed worse OS in patients with SM (HR 1.15, 95% CI 1.09–1.22, p<0.001). Median OS varied substantially by SM site (see Table). Conclusions: Our study demonstrates a substantial burden of SMs among patients with WM/LPL and are associated with substantially inferior survival despite the indolent nature of the disease. The marked heterogeneity in SM types and outcomes highlights the need for risk-adapted surveillance, survivorship-focused care, and equitable strategies to address disparities and improve long-term outcomes in this population. SM Site Median OS (years) IQR p-value Hepatopancreatobiliary 1 0 <0.05 CNS 3.5 9 <0.05 Breast 3 6 <0.05 Colorectal 4 3.5 <0.05 Lymph Node 5 8 <0.05 Blood 6 7 <0.05 Lung 7 9 <0.05 Head & Neck 6.5 8.5 <0.05 Melanoma 9 10 <0.05 Urogenital 10.5 7 <0.05

e19092 Background: Advances in immunochemotherapy and cellular treatment have improved outcomes for diffuse large B-cell lymphoma (DLBCL), but the population-level effect and equity of benefit are unclear. Understanding mortality trends and inequality is critical to developing targeted medicines. Methods: We used ICD-10 codes to assess DLBCL mortality from the CDC WONDER Multiple Causes of Death data (1999-2023). The age-adjusted mortality rates (AAMR) per 100,000 were calculated using the 2000 US standard population. Trends were assessed using Joinpoint regression to calculate annual percent change (APC) and average annual percent change (AAPC). Mortality was broken out by gender, race/ethnicity, age group, US Census area, and urban-rural categorization. Results: From 1999 to 2023, the national AAMR for DLBCL decreased from 3.8 to 2.5 per 100,000 (AAPC -2.1%) (p < 0.001). Non-Hispanic White patients saw the greatest decline (AAPC -2.5%), followed by non-Hispanic Black patients (AAPC -1.2%), resulting in increasing racial inequalities (rate ratio Black:White 1.35 in 2023 vs. 1.18 in 1999). Urban areas had much larger mortality decreases than rural areas (AAPC −2.3% versus −1.1%). Regional disparities were clear, with rates typically higher in the Southeast and Midwest. Inflection points were identified in 2006 and 2012, coinciding with widespread use of rituximab-based therapy and better availability of second-line medications. Conclusions: Although DLBCL mortality has decreased throughout the US over the last two decades, progress has been patchy, with significant racial and regional differences. Clinical Takeaway: Targeted interventions addressing access to therapy and early detection in high-risk populations are needed to close persistent DLBCL outcome gaps.

e19046 Background: While outcomes in pts with R/R FL have improved with current SOC treatments (Tx), there remains a need for safe, efficacious, and convenient Tx options. GOLCA is a potential, first-in-class, oral CELMoD designed for Tx of lymphoma, with preferential distribution to lymphoid organs and enhanced activity in lymphoma cell lines. GOLCA induces rapid and deep degradation of Ikaros and Aiolos, leading to direct cell killing and immunomodulatory activity. GOLCA + R was well tolerated and effective in heavily pretreated pts in the two-part Ph 1/2 study, CC-99282-NHL-001. Here, we provide longer f/u in pts with R/R FL from Part B of the study. Methods: Pts with R/R FL with ≥2 prior lines of Tx (≥1 if prior anti-CD20 Tx) received GOLCA orally, once daily at 0.2 mg (n=22) or 0.4 mg (n=38) ± R for up to 2 y or until progressive disease (PD)/unacceptable toxicity. Primary endpoints included safety and RP2D determination; secondary endpoints are preliminary efficacy and PK. Results: As of September 15, 2025, 60 pts were enrolled. In 0.2 and 0.4 mg groups, median prior Tx lines were 3 and 3, 32% and 32% had prior lenalidomide (LEN), 27% and 29% had prior T-cell–redirecting Tx (CAR T and/or bispecific antibody) and 32% and 32% were refractory to last regimen. Tx is ongoing in 6 (27%) and 17 (45%) pts at 0.2 and 0.4 mg, respectively; discontinuations (d/c) were mostly due to PD. Neutropenia, an on-target side effect of GOLCA, was the most common grade 3/4 Tx-emergent adverse event (TEAE) occurring in 59% and 68% of pts at 0.2 and 0.4 mg, followed by anemia (9% and 16%) and febrile neutropenia (9% and 8%). Median time to resolution of neutropenia was 8 days. Dose reductions occurred in 14% and 37% of pts at 0.2 and 0.4 mg, most commonly due to neutropenia (5% and 21%) and febrile neutropenia (5% and 5%). No d/c or deaths were from GOLCA-related TEAEs. Non-hematologic TEAEs were infrequent and mostly low grade. In efficacy-evaluable pts (GOLCA 0.2 and 0.4 mg + R, n=22 and n=36), median f/u was 14.03 months (mo), overall response rate (ORR) was 77% (complete response rate [CRR], 41%) at 0.2 mg, and 97% (CRR, 78%) at 0.4 mg. In the 0.4 mg group, responses were consistent in high-risk subsets including pts with prior LEN (ORR, 100%; CRR, 75%) and/or T-cell–redirecting Tx (ORR, 91%; CRR, 64%). GOLCA 0.4 mg + R demonstrated durable responses (median DOR, 9.17 mo; 91% of pts who achieved a CR remained in CR at cutoff). Conclusions: With longer f/u, GOLCA + R demonstrated promising efficacy with durable responses and no new safety signals. The 0.4 mg group had higher ORR and CRR than 0.2 mg, including in pts with prior LEN-based and/or T-cell–redirecting Tx, with a manageable safety profile at both doses. The results support the development of GOLCA + R as a fixed-duration, chemotherapy-free outpatient Tx in the Ph 3 GOLSEEK-4 study in 2L+ FL (NCT06911502). Clinical trial information: NCT03930953 .

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.

e16377 Background: 1L systemic treatment of mPDAC can lead to severe adverse events (AEs). To contextualize the safety profile of irinotecan-based regimens, real-world data were used to characterize AEs and their management in patients receiving 1L mPDAC treatment with FOLFIRINOX (FFX) or gemcitabine+Nab-paclitaxel (Gem+NabP). Methods: De-identified data from Mayo Clinic electronic health records (all sites; records collected 2010–2023) were used. Natural language processing was leveraged to confirm staging and metastatic classification and to extract treatment data. Adults with mPDAC with stage IV and/or TNM staging of M1 who received ≥ 1 dose of FFX or Gem+NabP were included. Primary endpoint: proportion of patients with AEs of interest (diarrhea, nausea, vomiting, neuropathy, and neutropenia) following initiation of 1L treatment. Secondary endpoints: proportion of patients who received treatment for each AE of interest, median time to resolution and treatment of each AE of interest, and proportion of patients who switched mPDAC treatment or had dose reductions due to AEs. Results: In total, 405 patients (FFX, 197; Gem+NabP, 208) were identified. The proportions of patients who experienced and were treated for any-grade AEs of interest are reported in the Table. Of the AEs of interest, neutropenia resolved most quickly (median time from onset to resolution, FFX: 9.5 days; Gem+NabP: 12.5 days); neuropathy took the longest time to resolve (FFX: 44.0 days; Gem+NabP: 74.0 days). Median time to AE treatment was shortest for nausea and vomiting (both 0.0 days for FFX and for Gem+NabP). Time to treatment was longest for neuropathy (FFX: 158.5 days; Gem+NabP: 70.0 days). Only 5.1% of patients on FFX and 13.4% on Gem+NabP received treatment for neuropathy. Of patients in the FFX group who switched/reduced treatment (n=140), 58.6% received a dose reduction and 7.1% switched to Gem+NabP due to AEs. Conclusions: At the Mayo Clinic sites, incidence of any-grade AEs associated with 1L mPDAC treatment were similar or higher than rates of any-grade or ≥ 2/3–4 grade AEs reported in the literature. Nausea, vomiting and diarrhea were the most commonly treated AEs for both irinotecan-based (FFX) and non-irinotecan-based (Gem+NabP) 1L regimens; neutropenia and neuropathy were less commonly treated. FFX dose reductions were commonly attempted before switching regimens. Proportion experiencing any-grade AE (AE incidence in the literature) Proportion experiencing AE treated for an AE FFX Gem+NabP FFX Gem+NabP Diarrhea 74.6% (50–80%, any grade) 43.8% (< 5%, any grade) 92.5% 56.0% Nausea 81.7% (45%, any grade) 72.1% (20%, grade ≥ 2) 98.8% 96.7% Vomiting 54.8% (10%, any grade) 42.8% (20%, grade ≥ 2) 98.1% 98.9% Neutropenia 58.9% (45%, grade 3–4) 48.1% (12–21%, grade 3–4) 62.1% 46.0% Neuropathy 59.9% (25%, grade 3–4) 32.2% (30%, grade 3–4) 5.1% 13.4%

e16334 Background: Liver cancer remains a leading cause of cancer-related mortality in the United States. Although overall mortality has increased over the past two decades, age-specific patterns and demographic disparities are not fully characterized. Here, we analyzed U.S. liver cancer mortality trends from 1999 to 2023, with a focus on age-related, racial and ethnic, and geographic differences. Methods: Mortality data for U.S. adults aged ≥25 years from 1999 to 2023 were obtained from the CDC WONDER database (ICD-10 codes C22.0–C22.9). Age-adjusted mortality rates (AAMRs) were standardized to the 2000 U.S. population. Joinpoint regression was used to estimate annual percent change (APC) and average annual percent change (AAPC) across age groups, sex, race/ethnicity, U.S. census regions, and levels of urbanization. Results: From 1999 to 2023, overall liver cancer AAMRs increased from 6.95 to 10.1 per 100,000. Marked age-specific differences were observed. Mortality among adults aged 45–54 and 55–64 years peaked in the mid-2010s and subsequently experienced significant declines through 2023 (recent APCs < −4.5% for both groups; P < 0.001). Specifically, while the overall AAPC for the 55–64 age group was +1.89%, mortality significantly reversed after 2016 (APC, −4.59%). In contrast, mortality continued to rise among older adults, including those aged 65–74 years (AAPC, +2.26%), 75–84 years (AAPC, +1.69%), and aged ≥85 years (AAPC, +1.77%) (all P < 0.001). Differences in mortality trends were also identified across racial and ethnic groups. Sustained increases were observed among Non-Hispanic White individuals (AAPC, +1.89%; P < 0.001), while Hispanic/Latino populations experienced declines after 2013 (APC, −0.67%; P = 0.003). Non-Hispanic Black individuals demonstrated a significant decrease in mortality between 2017 and 2020 (APC, −3.82%; P = 0.03). Regionally, liver cancer mortality declined in the Northeast after 2013 (APC, −0.66%; P < 0.001), whereas no significant post-peak declines were observed in the South or West. Conclusions: U.S. liver cancer mortality trends exhibit substantial heterogeneity by age, race and ethnicity, and geographic region. The recent, sharp declines among middle-aged adults (APCs < −4.5%) likely reflect the success of large-scale viral hepatitis screenings and highly effective antiviral therapies, whereas continued increases among older adults may relate to the cumulative impact of metabolic risk factors and delayed diagnosis. Persistent racial and regional disparities highlight the need for targeted, age-specific prevention and surveillance strategies.

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