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Importance If the success of Descemet membrane endothelial keratoplasty (DMEK) is not affected by whether the donor has diabetes, then the donor pool should expand. Objective To determine whether the 1-year DMEK success rate is affected by the presence of diabetes in the donor. Design, Setting, and Participants This was a multicenter, double-masked, randomized clinical trial conducted from February 2022 to July 2025 at 28 clinical sites (46 surgeons), with donor corneas provided by 13 eye banks in the US. Included in the study were individuals undergoing low to moderate risk DMEK (95% for Fuchs endothelial corneal dystrophy). Study data were analyzed from April to September 2025. Intervention DMEK performed with a cornea from a donor without or with diabetes, assigned using a minimization procedure (comparable with randomization) to achieve an approximate 2:1 distribution, respectively. Main Outcomes and Measures Graft success at 1 year Results A total of 1097 individuals (1421 study eyes; median [IQR] age, 71 [66-76] years; 631 female [57.5%]) were included in the study. The 1-year cumulative probability of graft success was 96.3% (95% CI, 95.0%-97.5%) among 912 study eyes (64.2%) receiving tissue from donors without diabetes and 97.1% (95% CI, 95.5%-98.4%) among 509 study eyes (35.8%) receiving tissue from donors with diabetes (difference between groups = 0.7 percentage points; 95% CI, −1.2 to 2.6; P = .63). The 1-year cumulative probability of graft success was 96.5% (95% CI, 93.6%-98.9%) in the mild donor diabetes severity subgroup (n = 173) and 97.3% (95% CI, 95.4%-98.8%) in the moderate to severe donor diabetes severity subgroup (n = 336), using a diabetes severity rating scale based on medical history. The rates of primary donor failure, early failure related to surgical complications, and subsequent failure were as follows: 2.5% (23 of 912), 0.7% (6 of 912), and 0.3% (3 of 912), respectively, in recipients of tissue from a donor without diabetes, and 2.6% (13 of 509), 0.4% (2 of 509), and 0%, respectively, among recipients of tissue from a donor with diabetes. There were no failures due to graft rejection. Conclusions and Relevance The 1-year success rate in eyes undergoing DMEK with successfully prepared tissue was very high regardless of donor diabetes status. These results, supported by the separately reported finding that endothelial cell loss and cornea morphometry after 1 year were not affected by donor diabetes status, provide strong support for having no restrictions on the use of tissue from donors with diabetes for DMEK. Trial Registration ClinicalTrials.gov Identifier: NCT05134480

Multiple myeloma (MM) treatment outcomes in developing countries may be impacted by resource constraints. This systematic review and meta-analysis evaluated efficacy outcomes of MM treatments across developing regions. Comprehensive searches in five major databases identified 37 eligible studies from Asia, Africa, Latin America, and Eastern Europe. The Newcastle-Ottawa Scale was used to assess risk of bias. Newer novel agents including daratumumab, carfilzomib, and pomalidomide showed limited use across studies. For patients receiving autologous stem cell transplantation (ASCT), the pooled overall survival rate at longest follow-up (2.5-12.5 years) was 62% (95% CI: 48-75%), with high heterogeneity (I²=92%), while the progression-free survival rate at longest follow-up (3-8 years) was 44% (95% CI: 23-67%). Comparative analyses demonstrated ASCT was associated with significantly superior 5-year survival compared to conventional chemotherapy (RR: 1.59; 95% CI: 1.38-1.82). Bortezomib-based regimens showed better outcomes than thalidomide-based therapies (HR for overall survival (OS) at 4 years: 0.73; 95% CI: 0.53-1.0) and alkylating agent-based regimens (HR: 0.48; 95% CI: 0.28-0.83). Despite resource limitations, ASCT and certain novel agents are associated with improved survival outcomes for MM patients in developing countries. However, substantial heterogeneity in outcomes suggests variability in healthcare infrastructure, treatment accessibility, and clinical expertise across these regions.

Bridging locoregional therapy (LRT) is widely used in liver transplant (LT) candidates with hepatocellular carcinoma (HCC) to minimize waitlist dropout and evaluate tumor biology. While transarterial chemoembolization (TACE) has historically been the predominant approach, the role of transarterial radioembolization (TARE) is expanding. Comparative effectiveness data for these 2 modalities as bridging strategies remain limited. This study assessed the trends, factors influencing therapy selection, and outcomes of transarterial bridging LRT. We conducted a retrospective cohort study of adult LT candidates with HCC listed in the Organ Procurement and Transplantation Network (OPTN) between 2016 and 2024 who received TACE or TARE as their sole bridging LRT. Inverse probability weighting (IPW) was applied to balance baseline covariates. Multivariable Fine–Gray competing risk regression and stratified Cox proportional hazards and logistic regression models were used to assess waitlist dropout, complete pathological necrosis (CPN), recurrence, and overall survival. Among 8367 patients, 5472 (65%) received TACE, and 2895 (35%) received TARE. TARE use increased significantly from 22.5% to 51.7% over the study period. TARE was more likely to be used among patients with MASLD, older age, and high tumor burden, and less likely in those with lower socioeconomic status. TARE recipients had a significantly lower risk of waitlist dropout (sHR 0.83, p <0.001) and a higher likelihood of achieving CPN (aOR 2.24, p <0.001). The overall survival did not differ significantly between groups (aHR 0.94, p =0.19). The use of TARE as bridging therapy in HCC LT candidates has surged and is influenced by socioeconomic factors, comorbidities, and tumor burden. TARE effectiveness has been demonstrated by its advantages in waitlist retention and tumor necrosis. Further studies are warranted to evaluate its impact on post-LT recurrence and to validate the cost-effectiveness among transarterial therapies.

ABSTRACT Introduction A novel therapy for heavily pretreated triple‐class–exposed multiple myeloma (TCE MM) is B‐cell maturation antigen (BCMA)‐targeted immunotherapy. While the number of TCE+BCMA‐exposed patients is growing, real‐world data for this group are limited. Methods We present real‐world data from patients with TCE+BCMA‐exposed MM who initiated a subsequent line of therapy (LOT) using a US‐based claims database, Komodo's Healthcare Map. Results We identified 656 TCE+BCMA‐exposed patients; mean age was 66.5 years. Time from MM diagnosis to index was 5.4 years; mean number of prior LOTs was 5.9. The most prevalent prior therapy received within each drug class was daratumumab (98.5%), pomalidomide (86.0%), carfilzomib (85.8%) and belantamab mafodotin (74.5%). A total of 137 different subsequent treatment regimens were observed following TCE+BCMA exposure; the most common regimen was teclistamab (10.4%). The top three targeted agents within the subsequent regimen were carfilzomib (20.2%), pomalidomide (20.1%) and bortezomib (16.6%). Among this TCE+BCMA‐exposed population who received subsequent treatment, the median time to next treatment or death was 6.8 (95% CI, 6.1–7.5) months; time to treatment discontinuation or death was 3.5 (95% CI, 3.2–3.7) months. Conclusion This first real‐world analysis of patients with heavily pretreated TCE+BCMA‐exposed MM shows poor clinical outcomes, frequent therapy retreatment and no standard‐of‐care, highlighting the need for novel treatments. Clinical Trial Registration The authors have confirmed clinical trial registration is not needed for this submission.

ABSTRACT The characteristics at diagnosis and clinical course of primary extranodal follicular lymphoma (EFL) have not been extensively described. The International Extranodal Lymphoma Study Group (IELSG) conducted an international retrospective survey aimed to describe the clinical features at diagnosis and the outcomes of FL cases with a clinically dominant extranodal component. The dataset included 605 pathologically reviewed cases from 19 different countries, and their outcomes were compared to those of nodal follicular lymphomas. The two most common presentation sites for EFL were the skin ( n = 334) and the gastrointestinal tract ( n = 72), with 22 cases having primary duodenal localization. These subsets exhibited unique features at diagnosis and significantly different overall survival (OS) patterns. After a median follow‐up of 5.5 years, primary cutaneous lymphomas showed a superior outcome [10‐year OS: 89% (95% CI, 83%–93%)], while primary gastrointestinal lymphomas had an intermediate outcome [10‐year OS: 79% (95% CI, 59%–90%)]. Among the gastrointestinal lymphomas, primary duodenal lymphomas tended toward the best outcome [10‐year OS: 95% (95% CI, 69%–99%)]. Other primary extranodal sites had inferior outcomes [10‐year OS: 59% (95% CI, 48%–68%)], similar to primary nodal lymphomas [10‐year OS: 57% (95% CI, 49%–64%)]. These findings support the identification of specific primary FL localizations as distinct entities with particular clinical and biological characteristics.

e20520 Background: Cancer and respiratory failure (RF) are amongst leading causes of mortality in adults. This study investigates national trends in age-adjusted mortality rates (AAMRs) for cancer and RF in the United States from 1999 to 2023, focusing on disparities by gender, race, region, and rural-urban residence to inform public health strategies. Methods: This descriptive study analyzed data from the CDC WONDER database, of adults aged 25 and older. Mortality data were identified using ICD-10 codes C00–C97 (cancer) and J96 (RF). AAMRs per 100,000 population were calculated and stratified by gender, race/ethnicity, census region, urban-rural classification, and state. Temporal trends were analyzed using Joinpoint regression to estimate annual percent changes (APCs) with 95% confidence intervals (CIs). Statistical significance was set at p < 0.05. Results: From 1999 to 2023, total deaths of 1,263,368 attributed to cancer and RF (682,141 men, 581,227 women). AAMRs declined from 1999 to 2004 (APC = -1.5, 95% CI: -4.0 to -0.4), stabilized from 2004 to 2012 (APC = 0.8, 95% CI: 0.1 to 2.4), and increased from 2012 to 2023 (APC = 3.2, 95% CI: 2.9 to 3.8). Men experienced a greater initial decline (APC = -2.1, 1999–2004) but significant increases thereafter (APC = 3.0, 2012–2023), while women showed a slower decline followed by sharper increases (APC = 3.5, 2013–2023). Non-Hispanic Black populations initially declined (APC = -1.7, 1999–2003) but later increased significantly (APC = 3.0, 2014–2020). Hispanic/Latino populations declined (APC = -1.2, 1999–2009) before rising sharply (APC = 3.1, 2009–2020). American Indian or Alaska Native populations showed consistent increases (APC = 1.7, 1999–2020). Urban areas experienced initial declines (APC = -1.7, 1999–2004), followed by increases (APC = 2.4, 2011–2020). Non-metropolitan areas exhibited steeper increases (APC = 4.6, 2014–2020). Regionally, the West recorded the highest AAMR (24.0), followed by the Northeast (23.6), South (20.9), and Midwest (18.0). Mississippi had the highest state-level AAMR (36.3), while Wisconsin had the lowest (10.0). States in the top 90th percentile included Mississippi, Arkansas, and California, while Wisconsin, Minnesota, and Oregon were among the lowest. Conclusions: Cancer and RF mortality declined initially but have significantly increased in recent years. Disparities persist across gender, racial, and regional groups, underscoring the need for focused public health efforts and equitable resource distribution to address these trends.

7527 Background: Etentamig (etenta) is a differentiated BCMA x CD3 bispecific T-cell engager composed of high avidity bivalent BCMA-binding domains, low-affinity CD3-binding domain designed to reduce cytokine release syndrome (CRS), and silenced Fc tail for extended half-life enabling convenient dosing. We present long term results from 2 ongoing Ph 1 studies evaluating efficacy and safety of etenta in patients (pts) with RRMM. Methods: Data were from a Ph 1 multicenter, open-label, dose escalation/expansion (NCT03933735) trial and Arm A of a Ph 1b, open label (NCT05650632) trial of etenta; both enrolled pts ≥18 years with RRMM, ≥3 prior lines of therapy (LoT), and triple-class exposed. Pts received 60 mg Q4W or 40 mg Q3W, both regimens with similar dose intensity, in the Ph 1 trial; pts from Arm A of the Ph 1b trial received a step-up dose (SUD) on day 1 and full dose of 60 mg Q4W on day 4. This pooled analysis assessed long-term efficacy, safety, and tolerability. Tumor response was assessed per IMWG 2016 criteria. Results: Of 146 pts with RRMM who received etenta, 87 (60%) were male, median age (range) was 68 (40–87) years, median prior LoT were 4 (3–23), and median duration of follow-up was 13 (1–48) months (mo). ORR was achieved in 96 (66%) pts and ≥VGPR in 79 (54%) pts. Response rates across subgroups are reported in the Table. Median duration of response was not reached (NR) (NR–NR) among responders; Kaplan-Meier (KM) estimate at 12 mo was 71% (58.5%–80.5%). Median PFS (mPFS) was NR (8.7–NR) mo; KM estimate at 12 mo was 55% (44.9%–63.1%). Any grade and G3/4 treatment emergent adverse events (TEAEs) occurred in 145 (99%) pts and 116 (79%) pts. Most common G3/4 TEAEs (≥15%) were neutropenia (38%), anemia (23%), lymphopenia (25%), and thrombocytopenia (16%). Infections G3/G4 were reported in 32 (22%) pts; most common infections G3/G4 (≥5%) were pneumonia (12%) and sepsis (5%). TEAEs leading to etenta discontinuation were reported in 13 (9%) pts. Deaths from TEAEs were reported in 13 (9%) pts; 10 were not attributed to etenta treatment. In Arm A of Ph 1 study where 60mg Q4W was administered with SUD and modified dex as premedication, CRS incidence was 30% (4% G2; No ≥G3 events) with median time to CRS onset of 22.3 (5.5–29.6) hours; and median time to CRS resolution of 20.7 (1.8–131.7) hours. Conclusions: Etenta with SUD demonstrated a low CRS incidence, durable response, and tolerability in pts with heavily pretreated RRMM. Efficacy across all subgroups was comparable and maintained, suggesting therapeutic benefits among a broad population and supporting further exploration in the ongoing Ph 3 Cervino study. Subgroup ORR, n (%) ≥VGPR, n (%) mPFS, months (range) Age ≥75years 26 (72) 23 (63.9) NR (7.5–NR) Race: Black 15 (63) 13 (54.2) 13.7 (5.0–NR) High cytogenetic risk 21 (55) 18 (47.4) 7.4 (2.8–NR) 3 prior LoT 29 (64.4) 23 (51.1) 13.5 (5.6–NR) ≥4 prior LoT 67 (67) 56 (56) NR (8.3–NR)

e16076 Background: Gastric cancer is the fourth leading cause of global cancer deaths. Despite declining incidence and mortality, it remains a significant contributor to the global disease burden. This study analyzes regional gastric cancer DALYs and mortality trends from 1990-2021 using the GBD database. Methods: The regional DALYs and mortality rates per 100,000 individuals aged 70+ from GBD 2021 were analyzed, with trends from 1990 to 2021 evaluated using AAPC, and statistical significance assessed by p-values. Results: In 2021, the greatest Age-standardized DALYs rates were recorded in Andean Latin America, with 3068.04 per 100,000; the lowest was found in High-income North America with 386.08 per 100,000. The most significant increase of DALYs rate from 1990 to 2021 was in Southern Sub-Saharan Africa, (AAPC = -0.3068%; 95% CI: -0.3852 to -0.2234; p < 0.000001), while in Western Europe, the largest decline was noted (AAPC = -2.9999%; 95% CI: -3.0164 to -2.9841; p < 0.000001). Andean Latin America was the region with the highest Age-standardized mortality rates (ASMRs) in 2021, at 207.58 per 100,000 while High-income North America had the lowest at 27.18 per 100,000. In Western Sub-Saharan Africa, the ASMRs were rising with an AAPC of -0.2601% (95% CI: -0.2872 to -0.2368; p < 0.000001), while Western Europe had the highest decline with an AAPC of -2.7658% (95% CI: -2.7895 to -2.7471; p < 0.000001). Conclusions: The global burden of diseases from 1990 to 2021 is regional in nature. In 2021, DALYs and mortality were predominantly high in Andean Latin America and East Asia and notably low in High-income North America. DALYs have risen across Southern Sub-Saharan Africa over three decades, and mortality increased over Western Sub-Saharan Africa, while both declined sharply in Western Europe. These trends underscore the importance of regionalized health solutions. DALY per 100,000. Metric Region 1990 2021 AAPC (1990-2021) HIGHEST DISABILITY-ADJUSTED LIFE YEARS (DALYS) PER 100,000 Andean Latin America 4469.23 3068.04 -1.14 East Asia 5507.72 2958.98 -1.99 High Income Asia Pacific 4849.23 2130.43 -2.71 LOWEST DISABILITY-ADJUSTED LIFE YEARS (DALYS) PER 100,000 High Income North America 758.59 386.09 -2.22 Australasia 1116.91 567.32 -2.16 South Asia 794.81 680.50 -0.46 HIGHEST MORTALITY RATE PER 100,000 Andean Latin America 293.65 207.58 -1.04 East Asia 324.60 188.92 -1.72 High Income Asia Pacific 316.44 161.94 -2.22 LOWEST MORTALITY RATE PER 100,000 High Income North America 51.24 27.19 -2.02 Australasia 74.36 41.81 -1.85 South Asia 47.50 41.95 -0.39

e16074 Background: Gastric cancer is a malignant disease characterized by the uncontrolled growth of cells in the stomach lining. It is a global health concern with regional variation in incidence and prevalence. This study examines the national mortality trends in adults aged 70 years and older from 1990 to 2021. Methods: GBD data was analysed to assess the mortality rates of Gastric cancer in individuals aged ≥ 70 years. The Estimated Annual Percentage Change (EAPC) was used to evaluate trends from 1990 to 2021, with p-values determining statistical significance. Results: From 1990 to 2021, the global prevalence of Gastric cancer increased, peaking in 2021. Japan recorded the highest prevalence (621.7379, UI: 525.93, 675.74), followed by the Republic of Korea and China.In 2021, Bolivia (Plurinational State of) had the highest mortality rate (309.7, CI: 400.9, 240.6), slightly lower than its 1990 rate (445.35, CI: 539.58, 362.14), which was the highest that year. Mongolia (303.15, CI: 378.8, 226.2) and Cabo Verde (265.1, CI: 322.6, 206.8) followed. The lowest mortality rates were observed in Morocco (20.9, CI: 25.9, 15.0), Namibia (20.93, CI: 25.93, 16.4), and Nigeria (23.27, CI: 32.3, 19.2).Countries with the largest EAPC increases included Egypt (0.98, CI: 1.84, -0.22), Honduras (0.31, CI: 0.7, -0.01), and Lesotho (0.16, CI: 0.597, -0.16). The greatest declines were seen in Austria (-0.72, CI: -0.68, -0.74), Czechia (-0.69, CI: -0.64, -0.74), and Hungary (-0.67, CI: -0.607, -0.72). Conclusions: Mortality rates associated with Gastric Cancer among individuals aged 70 and older increased globally from 1990 to 2021, notably in Egypt, Honduras and Lesotho, emphasizing the need for improved prevention, management, and research on underlying disparities. Mortality percent changes. Metric Region 1990 2021 EAPC with 95% CI (1990-2021) HIGHEST MORTALITY PERCENT CHANGE Egypt 30.43 60.44 0.98 (1.84, -0.22) Honduras 140.76 184.48 0.31 (0.7, -0.01) Lesotho 77.18 90.26 0.16 (0.59, -0.16) LOWEST MORTALITY PERCENT CHANGE Austria 177.25 49.48 -0.72 (-0.68, -0.74) Czechia 168.73 51.51 -0.69 (-0.64, -0.74) Hungary 184.88 60.55 -0.67 (0.607, -0.72)