Citations

8501 Background: TROPION-Lung02 (NCT04526691) evaluated the TROP2-directed antibody-drug conjugate (ADC) Dato-DXd plus pembro combination with or without Pt-CT in aNSCLC. Here we report primary analyses of pts receiving combination therapy in the 1L setting. Methods: Pts across 6 cohorts were dosed with Dato-DXd (4 or 6 mg/kg) plus pembro 200 mg alone (doublet) or with pembro plus Pt-CT (triplet; cisplatin 75 mg/m 2 or carboplatin AUC 5) Q3W. PD-L1 expression (tumor proportion score) was assessed locally by immunohistochemistry (22C3 assay). Primary objectives were safety and tolerability; efficacy was a secondary objective. Results: As of Apr 29, 2024, 96 pts received either the doublet (n=42) or triplet (n=54) combination as 1L therapy; 29% and 15% of pts were ongoing, respectively. Median ages were 65 (doublet) and 64 years (triplet). Median treatment durations were 9.7 and 5.8 months, respectively. Stomatitis (doublet, 57%; triplet, 33%) and nausea (doublet, 42%; triplet, 48%), primarily Gr 1–2, were the most common adverse events (AEs) across both regimens. Treatment related serious AEs occurred in 5 (12%) and 12 (22%) pts in each cohort and no deaths related to study drug were seen. Efficacy outcomes, including by histology, are summarized in the Table. Biomarker analyses, including efficacy by PD-L1 status, will be presented. Conclusions: In this largest data set to date evaluating an ADC combined with an anti-PD-1/L1 agent in the 1L setting, the combination of Dato-DXd plus pembro treatment both with and without Pt-CT elicited durable antitumor activity in pts with aNSCLC. Tolerability of the combinations was as expected, based on known profiles of the individual agents. Clinical trial information: NCT04526691 . All 1L (n=96) 1L, Nonsquamous (n=75) 1L, Squamous (n=21) Response, n (%) Doublet (n=42) Triplet (n=54) Doublet (n=33) Triplet (n=42) Doublet (n=9) Triplet (n=12) Confirmed objective response rate 23 (55) 30 (56) 17 (52) 24 (57) 6 (67) 6 (50) Complete response 1 (2) 2 (4) 1 (3) 2 (5) 0 0 Partial response 22 (52) 28 (52) 16 (49) 22 (52) 6 (67) 6 (50) Stable disease 14 (33) 18 (33) 12 (36) 14 (33) 2 (22) 4 (33) Progressive disease 3 (7) 2 (4) 3 (9) 1 (2) 0 1 (8) Disease control rate a 37 (88) 48 (89) 29 (88) 38 (91) 8 (89) 10 (83) Median duration of response, mo (95% CI) 20.1 (9.7–NE) 13.7 (5.7–NE) 24.9 (9.7–NE) 18.0 (8.0–NE) 12.0 (5.5–NE) 5.5 (4.1–NE) Median PFS, mo (95% CI) 11.2 b (8.2–21.3) 6.8 c (5.5–11.1) 11.2 (6.1–21.3) 10.8 (5.5–17.3) 10.2 (0.4–NE) 6.7 (1.0–8.2) a Proportion of pts with confirmed CR + PR + SD at 12 wks. b.c Median (95% CI) PFS follow-up, mo: b 17.3 (11.3−26.8); c 23.5 (17.3−27.9). mo, months; NE, not evaluable.

e19524 Background: Carfilzomib, a second-generation proteasome inhibitor, has emerged as one of the therapeutic agents in the treatment of relapsed or refractory multiple myeloma (MM). Despite its known cardiotoxicity, real-world data on its long-term cardiovascular outcomes remain limited. This study aimed to evaluate the real-world cardiovascular outcomes in patients with relapsed or refractory MM treated with carfilzomib. Methods: We utilized the TriNetX network to identify patients (≥18 years old) with relapsed or refractory MM between January 1, 2014, and January 1, 2019. We further categorized the patients into two groups: patients exposed to carfilzomib and patients not exposed to carfilzomib. Inclusion in the carfilzomib group required exposure to carfilzomib during the 5-year study period. Propensity score matching was performed to match these two groups based on comorbidities, medications, baseline hemoglobin A1c, low-density lipoprotein, and left ventricular ejection fraction to produce two comparable cohorts. The study outcomes were cardiovascular outcomes, including acute heart failure, acute myocardial infarction, cerebrovascular accident, acute venous thromboembolism, all-cause hospitalization, and all-cause mortality over the 5-year follow-up duration. Results: A total of 151,802 patients with relapsed or refractory MM were identified, including 6,386 patients (mean age 64.8 ± 10.6 years) who were exposed to carfilzomib and 145,416 patients (mean age 66.1 ± 12.7 years) who were not. After propensity score matching, there were 4,559 (65.3 ± 10.8 years of age, 44.7% female, 18.2% African American [AA]) patients who were exposed to carfilzomib and 4,559 patients who were not (65.2 ± 12.2 years of age, 45.1% female, 17.0% AA). Exposure to carfilzomib was associated with higher odds of acute heart failure (adjusted odds ratio [aOR]: 1.61; 95% CI: 1.48-1.77, P < 0.001), acute myocardial infarction (aOR: 1.24; 95% CI: 1.03-1.48, P = 0.020), cerebrovascular accident (aOR: 1.97; 95% CI: 1.47-2.64, P < 0.001), acute venous thromboembolism (aOR: 1.79; 95% CI: 1.58-2.03, P < 0.001), all-cause hospitalizations (aOR: 1.91; 95% CI: 1.75-2.09, P < 0.001), and all-cause mortality (aOR: 1.97; 95% CI: 1.80-2.16, P < 0.001). Conclusions: Patients with relapsed or refractory MM who were exposed to carfilzomib had poorer cardiovascular outcomes compared to those who did not.

e19515 Background: The prevalence of diabetes mellitus (DM) is significantly higher in patients with multiple myeloma (MM) compared to the general population. DM has been associated with worse outcomes in MM, including reduced overall survival and increased mortality. The impact of diabetes in patients with MM is further compounded by cardiotoxicity from proteasome inhibitors and the increased thromboembolic risk linked to immunomodulatory agents. Given the potential benefits of sodium-glucose cotransporter-2 (SGLT2) inhibitors, we hypothesized that their use in MM patients with DM could improve clinical outcomes and mitigate adverse events in this population. Methods: We utilized the TriNetX network to identify patients (≥18 years old) with MM and DM between January 1, 2013, and January 1, 2019. We categorized the patients into SGLT2 inhibitors users and SGLT2 inhibitors users. Inclusion in the SGLT2 inhibitors group required exposure to SGLT2 inhibitors for at least 1 year. 1:1 Propensity score matching was performed to match these two groups based on comorbidities, medications, baseline hemoglobin A1c, low-density lipoprotein, and left ventricular ejection fraction to produce two comparable cohorts. The study outcomes include all-cause mortality, all-cause hospitalization, acute venous thromboembolism (VTE), acute heart failure (HF), acute myocardial infarction (MI), cardiac arrhythmia, and cardiac arrest over the 5-year follow-up duration. Results: A total of 43,078 patients were identified, including 3,640 SGLT2 inhibitors users and 39,438 non-SGLT-2 inhibitors users. After 1:1 propensity-score matching, there were 3,379 SGLT-2 inhibitor users (68.9 ± 10.3 years of age, 38.0% female, 23.9% African American [AA]) and 3,379 non-SGLT-2 inhibitor users (68.9 ± 11.0 years of age, 35.9% female, 22.2% AA). SGLT-2 inhibitors users were associated with lower rates of all-cause mortality (odds ratio [OR]: 0.34, 95% confidence interval [CI]: 0.30-0.39) and all-cause hospitalization (OR: 0.52, 95% CI: 0.47-0.58). Lower odds of acute VTE (OR: 0.59, 95% CI: 0.49-0.70), acute HF (OR: 0.89, 95% CI: 0.81-0.98), acute MI (OR: 0.81, 95% CI: 0.69-0.95), cardiac arrhythmia (OR: 0.82, 95% CI: 0.70-0.97), and cardiac arrest (OR: 0.57, 95% CI: 0.44-0.74) were reported among SGLT-2 inhibitors users compared to non-SGLT2 inhibitor users. Conclusions: Our study revealed that only 8.4% of patients with DM and MM were prescribed an SGLT-2 inhibitor. Our study also demonstrated that SGLT2 inhibitor use was associated with lower odds of all-cause mortality and hospitalization, reduced risk of VTE, and favorable cardiovascular outcomes in this patient population.

e19538 Background: Patients with multiple myeloma (MM) and type 2 diabetes mellitus (T2DM) experience increased risks of morbidity and mortality. GLP-1 receptor agonists (GLP-1 RA) offer glycemic and cardiovascular benefits, but their impact on cancer-related outcomes is unclear. This study evaluates the association of GLP-1 RA therapy with clinical outcomes, MM-related biomarkers, and survival in MM patients with T2DM. Methods: We conducted a retrospective cohort analysis using the TriNetX network, including data from 104 healthcare organizations (2014–2019). Two cohorts were defined: (1) MM patients with T2DM starting GLP-1 RA therapy within three months of MM diagnosis and continuing therapy for at least one year (n=1,606 before matching), and (2) MM patients with T2DM not receiving GLP-1 RAs (n=40,306 before matching). Patients included were aged 18 years and older. One-to-one propensity score matching (PSM) balanced systemic MM therapy, BMI, and diabetes medications (e.g., insulin, metformin), yielding 1,279 matched pairs. Outcomes included five-year mortality, ICU and non-ICU hospitalizations, and MM-related biomarkers (hemoglobin, creatinine, neutrophils, and calcium). Most recent lab values were compared in the two groups. Statistical analyses included Kaplan-Meier survival estimates, hazard ratios (HR), risk differences, and T-Test statistics. Results: After PSM, baseline characteristics were well balanced. The mean age was ~ 66 years, white race was ~46%, females were ~ 40%, and hypertension was ~85%. Around 20% of MM patients received autologous transplants and ~27% received lenalidomide in the past. GLP-1 RA therapy was associated with less mortality (HR: 0.44, 95% CI: 0.36–0.54, P < 0.01), ICU admissions (HR: 0.59, 95% CI: 0.50–0.71, P < 0.01), and non-ICU hospitalizations (HR: 0.59, 95% CI: 0.53–0.65, P < 0.01). Patients on GLP-1 RAs had higher hemoglobin levels (11.61 ± 2.30 g/dL vs. 10.75 ± 2.47 g/dL, P < 0.01), with no significant differences in serum creatinine (119.068 µmol/L vs 115.648 µmol/L, P = 0.720) or neutrophils (P = 0.226). Patients who received GLP-1 RAs had higher serum calcium levels (9.17 mg/dL vs. 8.96 mg/dL, P < 0.01). GLP-1 RA use also decreased the incidence of septic shock (HR: 0.53, 95% CI: 0.44–0.64, P < 0.001) and pneumonia (HR: 0.59, 95% CI: 0.49–0.70, P < 0.001). Conclusions: GLP-1 RA therapy improves survival, reduces ICU and non-ICU hospitalizations, and lowers complications in MM patients with T2DM. Biomarker trends over five years suggest potential anticancer effects. Further research should explore whether GLP-1 RAs impact other malignancies, broadening their role in cancer therapy.

Précis: ASOCT features of greater bleb height, thicker bleb walls, and lower reflectivity are associated with trabeculectomy success, supporting the ASOCT’s utility in monitoring and predicting outcomes postsurgery through standardized imaging protocols. Purpose: To evaluate and quantify the relationship between bleb characteristics on ASOCT with surgical outcomes. Methods: A literature search was conducted across Medline, Embase, Cochrane, and Scopus for studies from the past 20 years, until 16 September 2024, on “glaucoma,” “trabeculectomy,” and “ASOCT.” Data collected included patient characteristics, each study’s definition of bleb success, clinical outcomes, as well as bleb characteristics. A literature review was conducted on studies that could not be used for meta-analysis. Results: Eleven studies, with a pooled total of 528 eyes in 517 patients, were included in the final meta-analysis. Successful blebs had significantly higher mean bleb height [mean difference (MD) 0.38 mm, 95% CI: 0.20-0.56 mm, P=0.002], greater maximum bleb wall thickness (MD: 0.21 mm, 95% CI: 0.07-0.35 mm, P=0.009), and decreased reflectivity (MD: −48.9%, 95% CI: −78.3 to −19.4%, P=0.010), compared with failed blebs. No significant differences were found in bleb fluid cavity height and bleb area. Narrative synthesis revealed that wider blebs, increased fluid-filled cavity height, increased number of microcysts, larger filtration opening widths, and multiform bleb walls were also associated with higher rates of bleb success. Early bleb parameters were statistically significant predictors of bleb success up to 12 months postoperatively. Conclusions: Greater bleb height, thicker bleb walls, and lower reflectivity on ASOCT are consistently associated with successful trabeculectomy outcomes. The ASOCT may be useful in predicting bleb success and in supplementing postoperative monitoring, hence guiding timely medical or procedural interventions, to ensure long-term bleb success.

Abstract Introduction: Breast cancer genome-wide association studies (GWAS) have identified over 200 susceptibility loci, many replicated in diverse populations. However, cross-ancestry evaluation of breast cancer genetic architecture remains limited. We examined breast cancer genetic architecture using GWAS summary results from European (EUR; cases (ca) = 188,474, controls (co) = 96,201), East Asian (EAS; ca = 20,393, co = 86,329), African American (AA; ca = 9,235, co = 10,184), and US Hispanic/Latina and Latin American (H/L; ca = 2,396, co =7,468) studies. Methods: GWAS results were derived from the Breast Cancer Association Consortium, the African Ancestry Breast Cancer Genetics Consortium (AABCG), Biobank Japan, and a meta-analysis of five studies of H/L women with breast cancer. Linkage disequilibrium (LD) scores were generated for EUR, EAS, and AMR using the 1000 Genomes Project, while AA LD scores were derived from a subset of AABCG controls. Heritability was estimated for each ancestry group using LD score regression. Genetic correlations between populations were assessed via Popcorn. Polygenicity was analyzed using GENESIS; however, due to the limited sample size in the H/L studies, these estimates were restricted to AA, EAS, and EUR. Enrichment of heritability across regulatory elements was evaluated using stratified LD score regression across all populations. Results: The logit-scale heritability and corresponding standard error (SE) were 0.466 (0.066) for EAS, 0.501 (0.050) for EUR, 0.588 (0.360) for H/L, and 0.614 (0.095) for AA. The estimated number of independent susceptibility loci was 4,446 for EAS, 5,235 for EUR, and 8,308 for AA. Using a clumping and thresholding approach, an optimal set of common variants were projected to explain 38.6% (EUR), 39.4% (EAS), and 26.2% (AA) of genetic variance for samples of 100,000 cases and 100,000 controls with AUCs from corresponding estimated polygenic risk scores (PRSs) of 0.621 (EUR), 0.634 (EAS), and 0.611 (AA). Genetic correlations were strongest between EUR and EAS (ρ = 0.79, SE = 0.08) and EUR and H/L (ρ = 0.68, SE = 0.21), and weakest between AA and EAS (ρ = 0.42, SE = 0.14) and AA and H/L (ρ = 0.26, SE = 0.24). Among 73 genomic features, we found significant (P &lt; 0.05/73) enrichment in heritability in EUR for ‘ancient promoter’ regions, transcription factor binding sites, H3K4me3, ‘super-enhancers’, H3K4me1, H3K27ac; in EAS for ‘super-enhancers’; and in AA for H3K27ac. No genomic features were significantly enriched in H/L, likely due to limited power. Conclusion: These findings suggest a shared breast cancer genetic architecture across diverse populations, as well as the potential for a similar level of breast cancer risk stratification by PRS in these populations. Expanding GWAS in underrepresented populations is essential to improve genetic risk predictions and foster equitable cancer prevention. Citation Format: James L. Li, Maria Zanti, Jacob Williams, Om Jahagirdar, Guochong Jia, Qiang Hu, Jean-Tristan Brandenburg, Li Yan, Weang-Kee Ho, Jingmei Li, José P. Miranda, Devika Godbole, Julie-Alexia Dias, Leila Dorling, Wenlong C. Chen, Nicholas Boddicker, Ying Wang, Alicia Martin, Martin J. Zhang, Yan Zhang, Joe Dennis, Esther M. John, Gabriela Torres-Mejia, Larry Kushi, Jeffrey Weitzel, Susan L. Neuhausen, Luis Carvajal-Carmona, Christopher Haiman, Elad Ziv, Laura Fejerman, Wei Zheng, Dezheng Huo, Douglas Easton, Nilanjan Chatterjee, Peter Kraft, Montserrat Garcia-Closas, Wendy Wong, Kyriaki Michailidou, Qianqian Zhu, Diptavo Dutta, Thomas U. Ahearn, Haoyu Zhang. Genetic architecture of breast cancer across diverse populations: Assessing heritability, genetic correlation, and polygenicity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2282.

ABSTRACTBackgroundChimeric Antigen Receptor (CAR) T‐cell therapy has arisen as a revolutionary treatment for hematologic malignancies. Our study aimed to evaluate how sex differences affect outcomes and complications following CAR T‐cell therapy.MethodsUtilizing the Nationwide Readmissions Database (2018–2020), we identified patients and divided them into male and female groups. Hospital outcomes and complications were compared among these two groups after propensity score matching to match groups based on comorbidities, producing two comparable cohorts.ResultsWe analyzed 2928 patients (1832 males, 62.6%, mean age 60.3 ± 13.7 years; 1096 females, 37.4%, mean age 59.1 ± 13.8 years). After propensity score matching (1:1ratio), 1092 males and females were compared. There were no significant sex differences in early mortality (adjusted odd ratios (aOR): 1.04 [95% CI 0.69–1.57]), 30‐day readmissions (aOR: 1.05 [95% CI 0.86–1.30]), or nonhome discharge (aOR: 0.89 [95% CI 0.60–1.31]). Females had higher odds of leukopenia (aOR: 1.26 [95% CI 1.06–1.50]) but lower odds of acute kidney injury (aOR: 0.68 [95% CI 0.52–0.88]).ConclusionsNo sex differences were found in hospital outcomes, including early mortality, 30‐day readmission, and nonhome discharge after CAR T‐cell therapy.

Diffuse large B-cell lymphoma (DLBCL) is the most prevalent and aggressive subtype of non-Hodgkin lymphoma comprising 30% to 40% of cases. While DLBCL frequently arises in the lymph nodes, up to 40% of cases originate in extranodal tissues. Primary splenic DLBCL is extremely rare comprising only ~1% of DLBCL cases and can be complicated by rare entities including gastrosplenic fistula (GSF). In contrast to DLBCL, polycythemia vera (PV) is a myeloproliferative malignancy. Polycythemia vera can transform into other hematologic malignancies including post-polycythemia myelofibrosis, but associations with DLBCL are uncommon. We present the first case of PV with concomitant primary splenic DLBCL complicated by GSF. While the majority of splenic lesions are benign, they have a broad differential diagnosis including malignant etiologies. Cystic or solid morphology, the number of lesions, and vascularity on imaging heavily guide further management. Due to concern for imminent massive upper gastrointestinal bleeding in the setting of GSF, our patient was diagnosed and managed with prompt splenectomy and gastrectomy. Percutaneous splenic biopsy is also a safe and effective diagnostic modality, but was deferred in our case given increased bleeding risk with PV. In conclusion, primary splenic lymphoma should be in the differential for a splenic mass regardless of whether the patient has a prior hematologic malignancy, and management should be prompt especially if complicated by a GSF.

ABSTRACTBackgroundMyeloproliferative neoplasms (MPN) are associated with an increased cardiovascular risk including acute coronary syndrome. However, there is a lack of comprehensive data regarding the rate of percutaneous coronary intervention (PCI), as well as the in‐hospital characteristics and outcomes for MPN patients.AimsWe aimed to evaluate the temporal trends and outcomes of PCI among patients with MPN.Methods and ResultsThe National Inpatient Sample database from 2016 to 2020 was queried to identify all PCI hospitalizations. Temporal trends and outcomes of patients with and without MPN following PCI were analyzed. Propensity score matching (PSM) was implemented to compare outcomes between MPN and non‐MPN groups. 2,237,210 PCI hospitalizations with 7560 (0.27%) patients with MPN were included in this study. Throughout the study period, the prevalence of MPN among PCI admissions remained stable (p‐value for trend = 0.12). Within the MPN subgroup, essential thrombocythemia (ET) was the predominant condition (53.2). Patients with MPN had higher prevalence of cardiovascular comorbidities than non‐MPN patients. Following PSM, MPNs were significantly associated with a higher risk of blood transfusions (OR: 1.66, 95% CI: 1.22−2.24, p = 0.001) and AKI (OR: 1.39, 95% CI: 1.17−1.65, p < 0.001). In contrast, the risk of in‐hospital mortality (OR: 1.18, 95% CI: 0.83−1.69, p = 0.354 and bleeding (OR: 1.43, 95% CI: 0.90−2.27, p = 0.127) did not significantly differ between the two groups.ConclusionsOur study demonstrated that while the prevalence of MPN among patients undergoing PCI remained stable, those with MPN faced higher risks of bleeding, blood transfusion and acute kidney injury. Further research is warranted to explore the underlying reasons for these increased risks and to improve outcomes in this high‐risk group.