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Association of immunotherapy infusion timing with outcomes in early-stage triple-negative breast cancer.

594 Background: Circadian regulation of immune function has been shown to influence the efficacy of immune checkpoint inhibitors (IO) in several malignancies. However, the clinical relevance of IO infusion timing in breast cancer remains unclear. We evaluated the association between IO timing, baseline characteristics, pathologic complete response (pCR), and recurrence outcomes in patients with early-stage triple-negative breast cancer (TNBC). Methods: We conducted a retrospective cohort study of 139 patients with early-stage TNBC treated at Manhattan and Mineola campuses alongside with four sites in Queens, Brooklyn, and Long Island using a KEYNOTE-522-based neoadjuvant regimen including pembrolizumab, chemotherapy, and surgery between July 2021 and June 2025. IO infusion timing was dichotomized using the cohort median time (12:22 PM); patients receiving all first three IO infusions after this cutoff were classified as late. Baseline characteristics including age, body mass index (BMI), race, ECOG performance status, clinical T/N stage, and chemotherapy backbone were compared between groups. pCR was defined as absence of residual invasive disease. Recurrence outcomes included local recurrence, distant recurrence, or death. Multivariable analyses adjusting for baseline clinical factors were performed. Results: Amongst our 139 patients, 108 received early IO and 31 received late IO. Patients receiving early IO were younger (mean age 55.9 vs 63.5, p = 0.025) and had lower BMI (27.4 vs 30.6, p = 0.017), while ECOG performance status 0-1 (early: 98.1% vs late: 90.3% respectively, p = 0.075), non-white race (52.5% vs 56%, p = 0.825), clinical T/N stage (T≥2: 88.7% vs 90.3%, p = 0.999; N≥1: 37.4% vs 38.7%, p = 0.999), carboplatin/paclitaxel chemotherapy backbone distributions (93.5% vs 90.3%, p = 0.693) were similar between groups. pCR occurred in 63% of patients receiving early IO and 45.2% receiving late IO (p = 0.098). Recurrence outcomes occurred in 3.7% of the early IO group and 16.1% of the late IO group (p = 0.026), driven primarily by distant recurrence (0.9% vs 12.9%, p = 0.009). After adjusting for age, BMI, and clinical T/N stage, late IO remained associated with distant recurrence (adjusted odds ratio 16.1; 95% CI, 1.39–186.4; p = 0.026). Conclusions: In this retrospective analysis, early IO infusion timing was associated with significantly lower recurrence risk, particularly distant recurrence. While pCR rates were not statistically significant between early vs late IO, we observed a numerical difference favoring early IO. These findings may suggest that circadian timing of IO may influence long-term outcomes beyond pathologic response. Given the retrospective design and limited number of events, these results are hypothesis-generating and warrant prospective validation.

Ethnicity-based comparative analysis of treatment endpoints of 30,000 HR+/HER2− metastatic breast cancer patients on CDK4/6 inhibitors (palbociclib/ribociclib/abemaciclib).

1085 Background: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i), in combination with endocrine therapy, are the mainstay for HR+/HER- metastatic breast cancer (MBC). However, ethnically diverse populations remain underrepresented in randomised clinical trials, limiting the ability to stratify by ethnicity. This meta-analysis utilises real-world evidence to compare treatment endpoints i.e., overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and adverse effects (AE) across ethnic groups. Methods: 116 studies from MEDLINE and Embase were included (Palbociclib: 67, Abemaciclib: 29, Ribociclib: 20). 31580 HR+/HER- MBC patients (Asian [AS]:22067; White [WH]: 8993; Black [BL]: 510) were included. Median survival and response rates were calculated using a random effects model to account for between-study variability. Parentheses represent 95% confidence intervals (CI). Results: Pooled analysis shows disparities in efficacy and significant variation in haematological toxicity. Maximum mOS benefit for AS was on palbociclib (61.8mo) whereas for WH was ribociclib (63.9mo), primarily driven by long-term follow-up in MONALEESA. mPFS benefit was longest in BL patients on abemaciclib (17mo), WH patients on palbociclib (27.7mo), AS patients on ribociclib (25.2mo). ORR was highest for ribociclib across all ethnic groups (Table). Meta-regression indicated ethnicity was not a significant independent moderator of AE risk (p > 0.05). AS cohorts demonstrated the highest incidence of Grade 3+ neutropenia across all agents: Palbociclib (72.0%; 49.5–87.1), Abemaciclib (52.8%; 46.1-59.4), and Ribociclib (45.8%; 39.1-52.5; p < 0.0001). In contrast, WH and BL patients exhibited significantly lower G3+ neutropenia rates, ranging from 12.0% to 33.8% (p < 0.0001). AS patients also showed the highest rates of leukopenia and anaemia across all CDK4/6i. Conclusions: Our large-scale meta-analysis findings establish a novel, evidence-based ethnicity-informed CDK4/6i selection framework to optimize treatment endpoints in HR+/HER2- MBC patients. This highlights the urgent need for prospective trials focused on underrepresented populations to close the survival gap. Metric Subgroup Palbociclib Abemaciclib Ribociclib ORR (%) AS 34.0 (27-42) 28.7 (16.1-41.3) 52.4 (46.4-58.5) WH 34.0 (28-65) 41.9 (14.9-68.9) 44.9 (32.1-57.7) BL 25.0 (17-23) N/A 34.6 mPFS (mo) AS 21.0 13.0 25.2 WH 27.7 21.8 24.1 BL 14.1 17.0 10.8 mOS (mo) AS 61.8 25.2 58.7 WH 60.5 37.6 63.9

Longitudinal epigenome-wide associations and pre-chemotherapy prediction of post-chemotherapy inflammation in patients with breast cancer undergoing chemotherapy.

e24094 Background: Inflammation is linked with cancer outcomes; systemic cytokine levels are associated with cognitive and functional impairments during chemotherapy. Epigenetic changes, such as DNA methylation, are also associated with cytokine levels, yet the relationship between epigenetic changes and inflammation during breast cancer treatment remains unclear. Methods: We performed epigenome-wide methylation association analyses to identify CpG sites whose DNA methylation levels were associated with circulating inflammatory cytokine concentrations in a nationwide cohort of 241 participants (192 patients with breast cancer and 49 age- and sex-matched healthy controls). DNAm was measured using Illumina 450K and EPIC arrays within 7 days pre-chemotherapy (Timepoint [T] 1) and within 1 month post-chemotherapy (T2). DNA methylation was analyzed on the M-value scale (log2 ratio of methylated to unmethylated probe intensities), allowing more stable variance for linear modeling. Cytokines measured from serum included IL-4, IL-6, IL-8, IL-10, and TNF-α, as well as soluble TNF receptors I and II (sTNFRI/II). Independent CpG-wise linear regression models were fit using limma, adjusting for age, group (chemotherapy vs control), and array type (450K vs EPIC). Analyses examined for cross-sectional associations between DNAm and inflammation at T1 and T2, as well as prediction of T2 inflammation from T1 DNAm. False discovery rate (FDR) < 0.05 defined epigenome-wide significance. Results: Across all analyses (N = 241; mean age = 60 ± 8 years; 78% college degree or above; 71% married/long-term relationship), we tested 449,521 CpG sites and identified five CpG–biomarker associations meeting FDR < 0.05. T1 DNAm at cg08458121 (chr17:1,028,676; CpG island within the gene body/5′UTR region of ABR) was positively associated with T1 IL-10 (log2) (T1→T1; β = 0.224, FDR = 0.032, N = 228). T2 DNAm at cg08458121 (chr17:1,028,676; CpG island within the gene body/5′UTR region of ABR) was positively associated with T2 IL-10 (log2) (T2→T2; β = 0.233, FDR = 0.026, N = 222), demonstrating consistent direction of association across timepoints. T2 IL-4 (log2) was positively associated with T2 DNAm at cg01963906 (chr1:27,677,240; intragenic CpG island in synaptotagmin-like protein 1 [SYTL1]; β = 0.126, FDR = 0.019, N = 222). In longitudinal prediction models (T1→T2), T1 DNAm was inversely associated T2 sTNFRI at cg01479664 (chr16:58,016,655; TEPP; N_Shore; β = −0.188, p = 1.6×10⁻⁷, FDR = 0.041, N = 222) and cg03198678 chr3:194,381,165; LSG1; OpenSea; β = −0.091, p = 2.1×10⁻⁷, FDR = 0.041, N = 222). Conclusions: This epigenome-wide analysis identified DNAm sites associated with circulating inflammatory biomarker levels at pre-chemotherapy and post-chemotherapy in breast cancer.

Carfilzomib-based combinations for Waldenström macroglobulinemia: Real-world experience from a single center.

e19080 Background: Waldenström Macroglobulinemia (WM) is the most common lymphoplasmacytic lymphoma (LPL). Bortezomib is a reversible inhibitor of the 26S proteasome and one of the mainstays of treatment for WM. One limitation in this therapy is peripheral neuropathy (PN) as an adverse effect, which can compound those patients with pre-existing IgM-associated neuropathy. Carfilzomib, a second-generation proteasome inhibitor has been used off-label for WM and carries less risk of PN but a small risk of cardiotoxicity. Methods: We performed a single-center retrospective study of patients seen at the John Theurer Cancer Center in Hackensack, NJ. We reviewed 43 records of patients with biopsy-confirmed WM treated with carfilzomib-based regimens from July 2012 to January 2026 under a protocol approved by our IRB. Outcomes included ORR per the 6th International Workshop on WM, progression-free survival (PFS) as time from first cycle to either progression of disease or death, overall survival (OS) using the Kaplan-Meier method, and relapse following treatment. PN, cardiac toxicity and discontinuation rates were collected. Results: 29 patients were male (67.4%), 40 were Caucasian (93%) and 3 were Asian (7.0%). Median values at diagnosis: hemoglobin 10.0 g/dL, platelets 227x10^9/L, beta-2-microglobulin 2.6 mg/dL, IgM 2408 mg/dL [IQR 973-5435]. Median age at treatment was 67.2 years. Revised IPSSWM risk stratification was calculable for 36 patients, of whom 12 were low-risk (33.3%), 17 were intermediate-risk (47.2%) and 9 were high-risk (25%). 10 had systemic amyloidosis. Bone marrow involvement was available for 37 patients with a median of 30% [IQR 20-60%]. Of the 36 patients tested, 33 had MYD88 p.L265P (91.7%). ORR was 40/43 (93%), and 32/43 were alive at last follow-up (74.4%) with median follow-up of 66.2 months. 24 patients were progression-free at 120 months (55.8%). In total, 3 patients had complete response (CR, 6.9%), 18 had partial response (VGPR, 41.9%), 18 patients had partial response (PR, 41.9%), 1 had minimal response (MR, 2.3%), 2 had stable disease (4.7%) and 1 had progression of disease (2.3%). Median IgM after treatment was 161.5 mg/dL [IQR 98-413]. 1 patient developed atrial fibrillation and 1 developed heart failure that resolved after carfilzomib withdrawal. 3 patients developed PN attributed to carfilzomib, 6 with pretreatment PN were diagnosed with IgM-associated neuropathy, 2 had anti myelin associated glycoprotein neuropathy and 1 developed PN after switching from carfilzomib to bortezomib. 2 patients stopped treatment due to toxicity, 1 cardiac and 1 non-cardiac. Conclusions: Carfilzomib-based treatment regimens are effective with a favorable safety profile in our population. One patient experienced characteristic cardiac toxicity and demonstrated full recovery of cardiac function. PN was attributable to carfilzomib in a small fraction of cases.

Impact of racial and socioeconomic factors on cutaneous B-cell lymphoma survival: A SEER analysis.

e19063 Background: Primary cutaneous B-cell lymphomas (PCBCL), primary cutaneous diffuse large B-cell lymphoma (PCDLBCL), follicle center lymphoma (PCFCL), and marginal zone lymphoma (PCMZL)—demonstrate distinct prognoses, yet population-level data on social determinants of health (SDOH) remain limited. This study evaluated the influence of demographic, socioeconomic, and geographic factors on survival across subtypes. Methods: We conducted a retrospective cohort study using the SEER-17 database to identify patients with PCDLBCL (ICD-O-3 9680/3), PCFCL (9597/3), and PCMZL (9699/3) restricted to primary skin sites. Variables included age, sex, race/ethnicity, median household income, and geography. Overall survival (OS) and cancer-specific survival (CSS) were evaluated using Kaplan-Meier methods and Cox regression (univariate and multivariate), with patients diagnosed through 2017 for ≥5-year follow-up. Analyses were performed in Python (v3.12) using lifelines and pandas, reporting hazard ratios (HRs) with 95% confidence intervals (CIs); p <0.05 was considered statistically significant. Results: A total of 4,525 patients were identified: PCDLBCL (n=1,744), PCFCL (n=751), and PCMZL (n=2,030). Age was the strongest predictor of survival across all subtypes; in PCDLBCL, patients aged ≥80 years had worse OS (univariate: median 24 vs. 65 months, HR 3.98; multivariate: HR 7.71; p0.001) and CSS (univariate: HR 2.26; multivariate: HR 4.57; p0.001) compared to patients aged 45-64 years, while in PCFCL, age was the only significant predictor (≥80 years: multivariate OS HR 20.60, CSS HR 12.57; p0.001). Male sex was independently associated with worse OS in PCDLBCL (HR 1.13, p=0.046) and PCMZL (HR 1.23, p=0.036). Racial disparities were significant only in PCDLBCL, with Asian patients demonstrating worse OS (univariate: median 40 vs. 65 months; multivariate: HR 1.52, p=0.007) and CSS (HR 1.34, p=0.001) compared to White patients, and American Indian patients showing worse OS (HR 2.49, p=0.032). Higher income (Q3 vs. Q1) was protective for OS in PCDLBCL (univariate: median 88 vs. 50 months; multivariate: HR 0.73, p=0.008) and for both OS (HR 0.62, p=0.028) and CSS (HR 0.38, p=0.021) in PCMZL. Geographic region significantly influenced OS in PCDLBCL (p=0.029) and PCMZL (p=0.001). No significant SDOH-related differences were observed in PCFCL. Conclusions: This population-based study demonstrates that SDOH differentially impact PCBCL subtypes. Age is the strongest independent predictor across all subtypes. PCDLBCL demonstrates the most pronounced disparities, with independent effects of race, income, sex, and geography. PCMZL shows socioeconomic and sex-based influences. PCFCL appears resistant to SDOH. These findings underscore the need for targeted interventions to address modifiable barriers in aggressive PCBCL subtypes.

Patient-reported experience of home-based oncology care among privately funded UK-based patients: Results from a multi-modal outreach survey.

e13603 Background: Home-based oncology services can reduce treatment burden, but patient experience data for privately funded cancer populations remain underreported in major oncology forums. We evaluated patient-reported experience, satisfaction and recommendation of a UK-based homecare oncology service to identify strengths and actionable service-improvement priorities. Methods: A cross-sectional patient experience survey was deployed to 1,100 privately funded oncology patients. Where an email address was available, invitations were issued by email; for non-responders and/or where no email address was available, two SMS reminders were sent at 7-day intervals after the initial invitation. Outcomes included overall satisfaction (CSAT), likelihood to recommend (NPS, 0–10), and free-text feedback coded into themes (overall positive/negative, clinical positive/negative, administrative positive/negative and improvement suggestions). Results: A total of 266/1,100 patients responded (24.2% response rate; typical response rate 5%). Overall satisfaction was high: 205/266 (77.1%) were extremely satisfied , 50/266 (18.8%) fairly satisfied , and 11/266 (4.1%) neutral or dissatisfied; Customer Satisfaction Score (CSAT) was 95.9% (and 98.5% when including neutral). Recommendation was also high with Net Promoter Score (NPS) 76.7 (n = 216 positives; n = 38 neutral; n = 12 negative). Free-text comments were provided by 192/266 respondents. The most frequent positive themes related to clinical care: clinical positive n = 98 (51%) and overall positive n = 137 (71%). Negative themes were concentrated in service processes rather than frontline care: admin negative n = 39 (20%) and overall negative n = 46 (24%), while clinical negative was less common (n = 15; 8%). Recurring improvement suggestions in comments included earlier/more reliable notification of visit times (e.g., narrowing the 2-hour window and confirming ETAs), improved scheduling/coordination, continuity of nursing staff, and reduction in medication/logistics errors or delays. Conclusions: Privately funded oncology patients based in the UK reported very high satisfaction and willingness to recommend home-based care, with feedback strongly endorsing frontline nursing quality. Opportunities to further improve experience are primarily operational: scheduling transparency (earlier confirmation and day-of-visit ETA), continuity, and tighter coordination across administrative functions and medication logistics. These findings support the acceptability of home-based oncology delivery while highlighting specific, actionable targets for service redesign. Additional study should be done with NHS-funded patients to confirm the experience of home-based oncology care to understand the impact across the patient population.

Real-world genetic testing patterns in prostate cancer assessed via artificial intelligence: Implications for NCCN guideline implementation.

5022 Background: Germline and somatic genomic testing in prostate cancer guide both targeted therapy selection and identification of heritable cancer risk. Although NCCN guidelines define testing eligibility based on disease risk and stage, real-world testing remains suboptimal. Population-level data indicate that only one-third of men with metastatic prostate cancer undergo genomic testing. As part of a larger effort to improve testing rates, we evaluated three consecutive years of prostate cancer care to quantify testing utilization and assessed artificial intelligence (AI) performance for risk stratification and testing eligibility. Methods: We conducted a retrospective chart review of patients with advanced prostate cancer treated at a large multi-site community oncology practice between 2023 and 2025. Clinical data were manually reviewed to assign disease stage, NCCN risk stratification, and eligibility for germline and somatic testing. In 2023, a rules-based AI applied explicit NCCN guideline logic (v1.2023). In 2024 and 2025, an untrained general-purpose AI model (ChatGPT 5.2) was provided NCCN guideline text (v1.2024 and v1.2025) and tasked with inferring risk category and testing eligibility. Primary outcomes included observed annual germline and somatic testing rates and AI concordance with manual review. Temporal trends in germline and somatic testing adoption were assessed using the Cochran-Armitage trend test. Results: Across 2023–2025, NCCN-indicated germline and somatic testing was inconsistently performed (Table 1), with significantly increasing rates from 2023 to 2025 (Cochran–Armitage trend test, germline p < 0.001, somatic p < 0.001). Testing outside of NCCN guidelines was ordered by clinicians in 10 (4%), 22 (9%), and 31 (18%) patients each year, respectively. Conclusions: In a large community oncology setting, NCCN-indicated germline and somatic testing for prostate cancer was frequently underutilized, despite significant improvement over time. Ongoing analyses seek to clarify which interventions contributed to increased testing rates and whether testing performed outside NCCN guidelines reflects broader clinical awareness of indications not consistently captured in structured data. AI-based guideline interpretation of NCCN guidelines demonstrated consistently high concordance with manual review and may offer a scalable approach to systematically identify patients eligible for genetic testing using structured data. Year Charts Reviewed Germline Eligible Germline Tested Somatic Eligible* Somatic Tested AI Risk Stratification AI Testing Recommendation Concordance 2023 259 194 54 (28%) 91 24 (26%) Not assessed Germline 97%; Somatic 100% 2024 255 195 82 (42%) 86 37 (43%) 235 / 255 (92%) Germline 100%; Somatic 100% 2025 177 167 98 (59%) 62 50 (81%) 177 / 177 (100%) Germline 100%; Somatic 100% *Somatic testing was “recommended” for patients with metastatic disease per NCCN 2023 -2025.

Benchmarking next-generation large language models (LLMS): Evaluation of patient-oriented prostate cancer guidance.

e17116 Background: Large language models (LLMs) are increasingly used by patients to seek medical information, including cancer-related guidance. However, the reliability and quality of LLM-generated responses for patient-oriented oncologic information remain insufficiently characterized. Early-stage prostate cancer (PCa) was chosen for evaluation due to its prevalence and preference-based treatment complexity that lead patients to seek outside information. We evaluated the performance of widely used LLMs in addressing patient-focused questions on early-stage PCa. Methods: We developed 47 questions based on National Comprehensive Cancer Network (NCCN) guidelines for patients on early stage prostate PCa, spanning seven clinical domains: general information, symptoms and risk factors, diagnostic testing, risk assessment, treatment options for early-stage disease, initial treatment for low-risk prostate cancer, and prostate-specific antigen (PSA) persistence and recurrence. Responses were generated using ChatGPT (GPT-5.2), DeepSeek (V3.2), and Gemini (2.5 Flash). Two board-certified oncologists independently evaluated each response for factual accuracy, clarity, coherence, relevance, and completeness using a 5-point Likert scale. Inter-rater reliability was assessed using Cohen’s kappa, and descriptive statistics were calculated for each LLM and domain. Results: Overall inter-rater agreement was low (κ = 0.05) across all domains. Despite this, all models achieved high absolute ratings, with mean scores ≥4.0 and median scores of 4–5 across most domains. ChatGPT demonstrated the highest performance across all quality domains, with mean ratings for clarity (4.68–4.89) and coherence (4.77–4.89) from both oncologists. Completeness scores were high for both ChatGPT (4.10–4.80) and Gemini (4.23–4.50). ChatGPT achieved the highest factual accuracy (4.10–4.90), followed by Gemini (4.18–4.75). Relevance ratings were similarly high for ChatGPT (4.34–4.90) and Gemini (4.45–4.52). Across clinical domains, ChatGPT and Gemini consistently achieved higher mean ratings than DeepSeek. ChatGPT showed the strongest performance for general information (4.0–5.0), symptoms and risk factors (4.73–5.0), risk assessment (4.75–5.0), and PSA persistence/recurrence (3.97–4.77). Gemini performed comparably across most domains, including diagnostic testing (4.49–4.73) and early-stage treatment (4.43–4.87). Conclusions: All evaluated LLMs provided generally high-quality responses to patient-oriented questions on early-stage PCa. However, poor inter-rater agreement highlights subjectivity in expert evaluation and underscores the need for standardized assessment frameworks. While ChatGPT and Gemini demonstrated greater consistency across domains, LLM-generated content should complement not replace clinician-guided patient education.

Integrated analysis of the ropeginterferon alfa-2b clinical program in essential thrombocythemia to demonstrate molecular and hematologic responses with safety profile information across treatment lines, ethnicities, and driver mutation types.

6576 Background: Patients with essential thrombocythemia (ET) have limited disease-modifying options. This integrated analysis of 182 ET patients from 2 trials evaluated consistency the efficacy of ropeginterferon alfa-2b (ropeg, BESREMi) across treatment lines and examined the impact of ethnicity and molecular subtype on outcomes. Methods: Data were pooled from the phase 3 randomized SURPASS-ET study (ropeg vs anagrelide [ANA] in HU-resistant/intolerant high-risk ET) and the phase 2b single-arm EXCEED-ET study enrolling both treatment-naïve and previously treated patients in North America. Endpoints included durable modified ELN response, hematologic and molecular responses, thrombotic events, and safety. Results: In SURPASS-ET, ropeg achieved a significantly higher durable modified ELN response at months 9 and 12 than ANA (42.9% vs 6.0%; p<0.0001), with superior platelet and WBC control, greater JAK2 V617F allelic burden reduction, and fewer major thrombotic events. In EXCEED-ET, durable objective modified ELN responses reached 60.2%, with ELN2009 molecular response rates of 35.0% for JAK2 V617F, 16.0% for CALR , and 25.0% for MPL, demonstrating consistent efficacy across treatment lines and mutation subtypes (Table 1). Safety profiles were comparable between studies, with mostly low-grade, manageable AEs. In the integrated analysis across studies, grade ≥3 TEAEs occurred in 28.6% of ropeg recipients and 33.8% of ANA. TEAEs leading to discontinuation (8.8% vs 20.0%) and serious AEs (12.6% vs 30.0%) were less frequent in the ropeg group. Fatal AEs occurred only in the ANA group (3.8%). Conclusions: Across the two studies, consistent molecular and hematologic efficacy with a favorable and manageable safety profile was demonstrated in treatment-naïve and pretreated ET populations, across ethnicities and disease drivers. These findings support ropeg as a disease-modifying treatment option with a favorable benefit–risk profile for all ET patients regardless of ethnicity, treatment line, driver mutation status, and mutational complexity. Clinical trial information: NCT04285086 , NCT05482971 . Key efficacy outcomes from both trials. Outcome SURPASS-ET EXCEED-ET RopegN=91 ANAN=83 RopegN=91 Durable modified ELN response, % Subgroup analysis by race, % (n)CaucasianAsianAfrican AmericanHispanicOther 42.920 (1/5)44.2 (38/86)--- 6.00 (0/2)6.2 (5/81)--- 60.257.2 (41/71)53.0 (4/7)100.0 (5/5)66.7 (2/3)100.0 (5/5) Platelet control ≤400×10⁹/L, % 56.0 21.7 48.4 WBC normalization, % 73.6 13.3 48.4 Molecular response*, % (n) JAK2 V617F 30.6 (19/62) 0 (0/42) 35.0 (7/20) CALR 30.0 (3/10) 0 (0/4) 16.0 (4/25) MPL 0 (0/1) 0 (0/1) 25.0 (2/8) Major thrombotic events, % 1.1 10.0 1.1 *The molecular response per the 2009 ELN criteria includes complete and partial responses.

Outpatient administration of cycle 1 of bispecific antibody therapy in hematologic malignancies: A real-world experience.

e19510 Background: Bispecific antibodies are increasingly used in hematologic malignancies but are commonly administered inpatient during ramp-up dosing of cycle 1 due to concerns for cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS). Inpatient administration increases healthcare utilization and may impact patient experience negatively. Real-world data supporting outpatient administration during cycle 1 are limited. Methods: At the Brown Cancer Center, we conducted a retrospective study of adult patients who initiated cycle 1 of bispecific antibody therapy as outpatient in the time period between January 2023 and December 2025. Agents included glofitamab, blinatumomab, teclistamab, and talquetamab. Outcomes included CRS, ICANS, hospitalization, treatment completion, mortality, and length of stay (LOS). Results: Of 70 patients screened, 18 received outpatient cycle 1 bispecific antibody therapy. Cytokine release syndrome occurred in 4/18 patients, all requiring hospitalization with a length of stay of 2 to 3 days. One patient developed ICANS, and one patient was hospitalized for a non– treatment-related reason. Based on manufacturer recommendations, the expected inpatient monitoring would be as follows for each drug: (teclistamab: 6 days, talquetamab: 8 days, blinatumomab: 3 days, glofitamab: 1 day). For our 18 patients, it will translate to 97 hospital days. The actual number of hospitalization days was 14, resulting in net savings of 83 hospital admission days. All patients completed cycle 1 therapy. No grade ≥3 toxicities or treatment-related deaths were observed. Conclusions: Our study showed that giving bispecific antibodies to patients in an outpatient setting during the first treatment cycle was safe and practical, with structured monitoring. Overall, the side effects from treatment were manageable. This approach can lead to cost savings, decreased hospitalization (85% reduction in LOS), and possibly higher patient satisfaction. Still, larger studies are needed to better select patients, improve predictions for side effects, and further clarify the safety of administering bispecific antibodies on an outpatient basis. Outpatient bispecific therapy. Therapy Patients (n) ICANS CRS Grade 1–2 Number of patients admitted within 30 days Recommended Inpatient Days (Cycle 1, per patient) Hospital Days Saved (Manufacturer-Recommended/Outpatient Days) Glofitamab 1 0 0 0 1 1/1 Blinatumomab 6 0 3 3 3 10/18 Teclistamab 5 1 0 2 6 27/30 Talquetamab 6 0 1 1 8 45/48 CRS: Cytokine Release Syndrome. ICANS: Immune Effector Cell-Associated Neurotoxicity Syndrome.

Clinical and genomic predictors of outcomes in patients (pts) with advanced urothelial carcinoma (aUC) treated with enfortumab vedotin and pembrolizumab (EVP): UNITE study analysis.

4560 Background: EVP is the recommended 1 st line (1L) therapy for pts with aUC and is moving into the perioperative setting. There is limited understanding of clinical factors and biomarkers predictive of EVP outcomes. Methods: We analyzed pts with aUC treated with EVP in the multi-site retrospective UNITE study. χ 2 test and logistic regression were used to assess observed response rate (ORR) and disease control rate (DCR). Log-rank test and Cox proportional hazard models were used to assess progression-free survival (PFS) and overall survival (OS) from EVP start. Multivariable analysis (MVA) included age, sex, race, ECOG performance status (PS), neutrophil-to-lymphocyte ratio (NLR), albumin, hemoglobin (Hgb), primary tumor site, histology, treatment line, and metastatic sites as covariates. Results: A total of 521 pts with aUC from 16 sites received EVP. Median age was 71, 75% were male, 81% were Caucasian, 76% had ECOG PS 0-1, and 72% were treated with 1L EVP. 74% had lower tract primary tumor, 65% pure urothelial histology, 18% liver metastases (mets), 43% non-liver visceral mets, and 28% lymph node (LN)-only mets. At 8.1 mos median follow-up from EVP start, the overall cohort had ORR 55%, DCR 82% [16% complete response (CR), 39% partial response (PR), 27% stable disease (SD)], median PFS (mPFS) 6.5 mos, and median OS (mOS) 19.8 mos. For 1L EVP pts, at 9.8 mos median follow-up, ORR was 59%, DCR 83% (20% CR, 39% PR, 24% SD), mPFS 10.1 mos, and mOS 23.3 mos. In both the overall cohort and 1L EVP pts, clinical factors associated with longer PFS and OS included ECOG PS 0-1, Caucasian race, albumin ≥ 3.5 g/dL, Hgb ≥ 10g/dL, NLR < 5, and absence of visceral mets. CR was associated with ECOG PS 0-1 (OR 3.6, 95% CI 1.4-12.5, p = 0.02), Hgb ≥ 10g/dL (OR 2.3, 95% CI 1.2-4.8, p = 0.02), NLR < 5 (OR 2.7, 95% CI 1.5-5.3, p = 0.002), LN-only mets (HR 3.8, 95% CI 1.7-9.8, p = 0.003), immunotherapy-naive status (OR 4.1, 95% CI 1.4-17, p = 0.02), and 1L EVP for aUC (OR 3.3, 95% CI 1.7-7.3, p = 0.001). Pts with CR had longer mPFS than pts with PR or SD (26.5 vs. 14.5 vs. 7.5 mos, p < 0.001) and longer mOS (NR vs. 33.4 vs. 14.5 mos, p < 0.001). Among 315 pts with molecular profiling, the most common alterations were in TERTp (55%), TP53 (45%), FGFR3 (22%), ARID1A (19%), KMT2D (18%), PIK3CA (18%), and CDKN2A/B (17%). In MVA, KMT2D alterations were associated with lower CR rate (6% vs. 19%, p = 0.05), shorter mPFS (5.0 vs. 8.0 mos, p = 0.04), and shorter mOS (12.0 vs. 20.0 mos, p = 0.04). Very high tumor mutational burden (≥ 15 mut/Mb) was associated with higher DCR (97% vs. 79%, p = 0.04) but no significant difference in PFS or OS. Conclusions: In this large real-world cohort, ECOG PS, metastatic site, treatment line, and prior immunotherapy exposure were associated with EVP outcomes. KMT2D -altered aUC may represent a high-risk molecular subset with worse outcomes. Further validation in prospective cohorts is needed.

When does time become a burden? Evaluating the association between time spent on cancer care and patient distress.

11057 Background: While cancer care is time-intensive, the specific impact of various tasks on patient well-being is poorly understood. We evaluated how time spent on specific cancer-care tasks contributes to patient distress and identified patient populations most vulnerable to these time burdens. Methods: We enrolled individuals receiving treatment for advanced-stage ovarian or metastatic breast cancer at the University of Minnesota and the University of Alabama-Birmingham. Participants used a mobile app for 28 days to log time spent on out-of-home and at-home cancer-care related tasks. Daily distress was measured via the National Comprehensive Cancer Network (NCCN) Distress Thermometer (0-10; 0=no distress, 10=extreme distress). The primary outcome was clinically significant distress (NCCN distress score <4 vs. ≥4). Predictors included any time spent on each task type on a given day for both out-of-home healthcare tasks (lab, clinic, treatment, research, imaging, other) and at-home tasks (taking medications, scheduling appointments, managing medical bills/insurance claims, symptom management, monitoring health status, seeking information, and arranging help/transportation). A multi-level model with a random intercept for participants was used, adjusting for age, employment, education, dependent and partner status. Odds ratios and 95% confidence intervals are reported. Results: Analysis included 1,869 days from 60 participants (median age 59; 42% employed; 35% with dependents). Experience of significant distress was more likely on days including out-of-home treatment compared to days without treatment (OR: 2.54 [1.47, 4.39]). Participants were also more likely to experience significant distress on days including time spent on symptom management (OR: 2.59 [1.85, 3.64]), health monitoring (OR: 2.50 [1.56, 3.98]), and managing bills/claims (OR: 2.24 [1.22, 4.12]) compared to days without those tasks. Vulnerability varied: employed patients were more distressed by managing bills/claims and information seeking, while non-working patients experienced more distress on treatment days. Among those with dependents, scheduling was a unique stressor. Conclusions: Out-of-home treatment and at-home cancer-care tasks are significantly associated with patient distress. Findings suggest that interventions reducing at-home administrative and symptom burdens would reduce patient distress, and resources may need to be tailored based on employment and caregiving status. Clinical trial information: NCT05708703 .

Impact of the geographic redistribution of MMaT-3 policy on regional and socioeconomic disparities in hepatocellular carcinoma transplantation.

e23242 Background: The MMaT-3 (Median MELD at Transplant minus 3) policy was implemented in 2019 to reduce geographic variation in liver transplant access by prioritizing candidates whose MELD scores approached local transplant thresholds. Although intended to promote regional equity, its impact on geographic performance and socioeconomic disparities among hepatocellular carcinoma (HCC) candidates remains unclear. Methods: Using UNOS/OPTN registry data, we conducted a retrospective analysis of adult HCC candidates listed during symmetric 21-month periods before (n = 4,630) and after (n = 4,049) MMaT-3 implementation. Time to deceased donor liver transplantation (DDLT) was assessed using adjusted restricted mean failure time (RMFT). Policy-associated changes in wait time were compared across geographic regions, race/ethnicity, and insurance status, using White race, private insurance, and the Southwest as reference groups. Results: Overall, MMaT-3 was associated with reduced system efficiency. Adjusted RMFT increased for White candidates (+25.5 days, p < 0.001) and privately insured candidates (+23.7 days, p < 0.001) compared with the pre-policy period. Regional effects were heterogeneous. Geographic disparities narrowed primarily due to worsening outcomes in historically high-performing regions rather than improvements in the most disadvantaged areas. New England (+68.3 to +78.7 days, p < 0.001) and New York (+61.1 to +52.7 days, p < 0.001) did not significantly improve and remained the most disadvantaged regions. The Southeast (approximately −160 to −60 days; policy-associated prolongation > 100 days, p < 0.001) and Midwest (approximately −80 to −20 days; prolongation ~60 days, p < 0.001) experienced substantial deterioration. The Mid-Atlantic (−29.8 to +14.4 days, p < 0.01) and Texas (−3.9 to +51.6 days, p < 0.001) shifted from neutral or favorable to significantly longer wait times. Despite regional stagnation, sociodemographic disparities improved. Pre-policy disadvantages among Black (+15.9 days) and Hispanic (+27.8 days) candidates were eliminated post-policy ( p ≤0.006), as were disparities among publicly insured candidates (+16.8 to +1.6 days, p < 0.001). Among Asian candidates, a substantial pre-policy disadvantage (+65.8 days) was reduced, though a residual disparity persisted post-policy (+39.7 days, p < 0.001). Conclusions: MMaT-3 was associated with reductions in racial and insurance-based disparities among HCC candidates but achieved geographic equity largely through deterioration in previously advantaged regions, with limited benefit for the most disadvantaged areas. These findings highlight trade-offs inherent in spatial allocation reforms and inform subsequent policy modifications.

Multidisciplinary onco–critical care management: Clinical impact.

e13568 Background: Advances in cancer diagnosis and treatment have increased survival, resulting in a growing number of patients (pts) at risk of acute, life-threatening complications requiring ICU evaluation. Although ICU admission was historically considered of limited benefit in oncology, recent evidence shows that selected pts with good functional status and potentially reversible conditions have outcomes comparable to non-oncological pts. Multidisciplinary ICU–Oncology committees may optimize patient selection, define appropriate therapeutic ceilings, and support individualized, evidence-based decision-making. Methods: Single-center, retrospective observational study at Juan Ramón Jiménez University Hospital (Huelva, Spain) after implementation of a multidisciplinary Onco–Critical Care Committee. Adult hospitalized patients with solid tumors evaluated between June 1 and December 31, 2025 were included. Demographic, oncologic, functional, ICU-related variables, and outcomes were collected. Prognostic factors were reviewed to guide ICU admission suitability. Descriptive analysis was performed using SPSS v21. Results: 55 pts were analyzed; median age was ~65 years and 60% were male. Most pts had good or intermediate functional status (ECOG 0–2: 87%), advanced disease (stage IV: 62%), and an estimated survival > 1 year (73%). Lung (21,8%), colorectal (12,7%), and breast cancers (10,9%) were the most frequent tumors. Main reasons for evaluation were cancer-related complications and treatment toxicity. The committee classified 56.6% as ICU candidates without limitations and 18.9% with limitations; 21.8% were ultimately admitted to ICU. Among ICU-admitted patients, illness severity was moderate (mean APACHE II 19.4), with frequent need for organ support. ICU survival was high (90%), while overall hospital mortality was 33%. Post-ICU syndrome was observed in approximately half of survivors. (Table 1). Conclusions: The implementation of a multidisciplinary Onco–Critical Care Committee enabled structured, individualized, and anticipatory decision-making regarding ICU admission in oncology patients. This collaborative approach facilitated appropriate patient selection, optimized use of critical care resources, and was associated with high ICU survival, underscoring the clinical value of integrating oncology and critical care teams in routine practice. Baseline characteristics and clinical outcomes. Variable Value Tumor TypesLungColorectalBreastProstate 21.8%12.7%10.9%7.3% Treatment modalityRadical intentPeroperative intentPalliative intent 20%28%45.5 % ICU supportMechanical ventilation (%)Vasopressors use (%)Renal replacement therapy (%) 33%50%50%

Clinical impact of germline <i>BRCA1/2</i> variants on breast and ovarian cancer management in a resource-limited setting: Real-world data from Thailand.

e22654 Background: Identification of germline BRCA1/2 variants is critical for guiding the management of breast and ovarian cancer, including surveillance, prophylactic surgery, targeted therapy, and prevention. However, data regarding the clinical implementation of these strategies in resource-limited settings remain scarce. We aimed to evaluate the real-world clinical impact of BRCA1/2 status on patient management—specifically surveillance, risk-reducing surgery, and PARP inhibitor utilization—at a major tertiary center in Thailand. Methods: We performed a retrospective analysis of electronic medical records for index patients with breast cancer who underwent germline genetic testing at Siriraj Hospital, Bangkok. We assessed clinical outcomes among patients identified with pathogenic or likely pathogenic (P/LP) BRCA1/2 variants. Data collection included operative history, pathology, imaging utilization, and systemic therapy. Key endpoints were the utilization rates of breast MRI, contralateral prophylactic mastectomy (CPM), risk-reducing bilateral salpingo-oophorectomy (rrBSO), and poly (ADP-ribose) polymerase (PARP) inhibitors. Results: Of 6,138 patients undergoing germline genetic testing, 278 (4.5%) harbored P/LP BRCA1/2 mutations. Among carriers with non-metastatic disease (n=253), genetic results were available pre-operatively in only 38% of cases, limiting immediate surgical decision-making. In the specific subgroup of non-metastatic carriers with &gt;3 years of follow-up (n=81; median follow-up 4.7 years), 41% underwent contralateral prophylactic mastectomy (CPM). In contrast, high-sensitivity surveillance was minimal: 2% underwent breast MRI monitoring, with the remainder relying on mammography and ultrasonography. For ovarian cancer risk reduction among patients aged ≥40 years, 85% received a gynecologic consultation, and 63% successfully underwent risk-reducing bilateral salpingo-oophorectomy (rrBSO). In the metastatic setting (n=42), PARP inhibitors were used in 19% of cases (n=8), with cost being the most frequently cited barrier to access. Conclusions: While the prevalence of BRCA1/2 mutations in this Thai cohort mirrors international data, clinical management deviates significantly from Western guidelines due to resource constraints. Specifically, access to high-cost surveillance (MRI) and targeted therapies (PARP inhibitors) remains minimal. These findings highlight a critical need to improve pre-operative testing turnaround times and address the financial toxicity that restricts access to standard-of-care therapies in resource-limited settings.

Liquid structure dependence of rapid crystallization dynamics for rare-earth terbium

Unveiling the phase transformation mechanism for liquid rare-earth metals has been a great challenge, especially at the metastable undercooled state. Here, the liquid structure dependence of the crystallization mechanism of rare-earth terbium was investigated by electrostatic levitation experiments and molecular dynamics simulations. After achieving a maximum liquid undercooling of 206 K (0.13Tm), the thermophysical prosperities including liquid density, surface tension, viscosity, and self-diffusion coefficient were determined over a wide temperature range. The strong chemical affinity created active substrates, introducing a scenario of heterogeneous nucleation associated with interfacial energy reduction. Furthermore, dendrite growth velocity exhibited a power law relation vs undercooling, consistent with the dendritic model accounting for nonequilibrium atomic attachment. Upon cooling, the thermal evolution and electronic distribution were intrinsically coupled with the enhancement of local topological order, characterized by fivefold symmetric and crystalline configurations. These findings clarified the correlation between liquid property and atomic arrangements, providing insights relevant to advanced functional materials.

Green-synthesized silver and zinc oxide nanoparticles: A mini review of antibacterial and antimycobacterial activities

Tailoring Solvation Structure via Soft‐Hard Segment Synergy in Gel Polymer Electrolytes Enables Dendrite‐Free Sodium Batteries with Ultra‐Long Cycling

ABSTRACT The development of polymer electrolytes with high ionic conductivity, robust mechanical strength, and excellent interfacial stability remains a critical challenge for high‐performance sodium metal batteries (SMBs). Herein, a “chemical‐structural dual regulation” strategy introduces complementary soft and hard segments into a gel polymer electrolyte (GPE), enabling concurrent optimization of solvation structure and mechanical properties. Soft segments with strong electron‐withdrawing ‐CF 3 groups form solvent‐rich domains that weaken Na + ‐solvent interactions, while amide N–H groups create polymer‐rich domains that enhance mechanical strength and anchor anions via hydrogen bonding, promoting sodium salt dissociation. Benefiting from this rational molecular design, GPE‐9 delivers an outstanding ionic conductivity of 1.11 mS cm −1 and a high Na + transference number of 0.74 at room temperature, and supports long‐term cycling of Na||Na symmetric cell at 0.2 mA cm −2 for 7000 h. The Na|GPE‐9|Na 3 V 2 (PO 4 ) 3 (NVP) cell demonstrates excellent rate durability, sustaining 12 000 and 20 000 cycles at 5C and 10C, respectively, with nearly 100% Coulombic efficiency. Furthermore, a 29‐layer pouch cell with NVP cathode and hard carbon (HC) anode delivers a high capacity approaching 1.0 Ah. This study demonstrates that designing polymer segments capable of regulating solvation structure and directing interfacial fluorination offers a promising strategy for high‐performance GPEs for Na batteries.

Real-world treatment and survival outcomes for zanubrutinib (zanu) and acalabrutinib (acala) monotherapy among treatment-naive patients with chronic lymphocytic leukemia (CLL) in the United States.

7045 Background: Bruton tyrosine kinase (BTK) inhibitors are central to the management of CLL/SLL (hereafter referred to as CLL). Acala was approved for CLL in the US in 2019, followed by zanu in 2023. Despite their widespread use, real-world evidence comparing therapy effectiveness is limited. This US-based study compared the real-world effectiveness of zanu and acala monotherapy as first-line treatment for patients with CLL based on overall survival (OS) and time to next treatment (TTNT). Methods: This retrospective analysis utilized the Komodo claims database between January 2015 and August 2025. Eligible patients were adults (aged ≥18 years) in the US with ≥2 diagnoses of CLL or SLL, who were treatment naive for CLL and had an index claim for monotherapy with zanu (January 2023 to August 2025) or acala (November 2019 to August 2025). The index date was defined as the date of the first observed claim for the respective therapy. Patients were required to have continuous enrollment or activities within 1 year prior to and 3 months after the index date. Patients with evidence of clinical trial participation, prior CLL/SLL treatment, or two diagnoses of mantle cell lymphoma between January 2015 and the index date were excluded. Outcomes included OS (measured from index claim to all-cause mortality), and TTNT (measured from index claim to initiation of subsequent therapy or death). If death did not occur, patients were censored at the date of last activity or the enrollment end date. For OS analysis, Komodo data captured the death date, but not the cause of mortality. Survival analyses were conducted using Kaplan-Meier estimates and Cox proportional hazards models. Inverse probability of treatment weighting (IPTW) was adjusted for age, sex, US region, treatment initiation year, and Charlson Comorbidity Index (CCI). Results: Among 16,788 patients (zanu, n=5819; acala, n=10,969), median age was higher in zanu (73.3 years) vs acala (71.8 years) cohorts. Most patients were male (acala, 62%; zanu, 59%), non-Hispanic white (acala, 73%; zanu, 72%), and the median CCI was 2 in both cohorts. Median follow-up was 12.8 and 16.4 months for in zanu and acala cohorts, respectively. Median TTNT and OS were not reached for either cohort. With the unadjusted model, zanu had a longer TTNT (unadjusted HR, 0.88; 95% CI, 0.79-0.97; P =.009) and OS (HR, 0.72; 95% CI, 0.62-0.82; P &lt;.001). After IPTW adjustment, zanu was associated with a significantly improved OS (IPTW-adjusted HR, 0.75; 95% CI, 0.65-0.86; P &lt;.001) and TTNT (IPTW-adjusted HR, 0.89; 95% CI, 0.80-0.98; P =.02) compared with acala. Conclusions: In this real-world analysis, zanu monotherapy demonstrated significantly longer TTNT and improved OS compared with acala monotherapy. These findings suggest that zanu may offer superior outcomes in the real-world setting.

Association between depth of IPRO-α response and overall survival (OS) in patients with advanced non–small cell lung cancer (aNSCLC) treated with first-line (1L) pembrolizumab monotherapy.

e20521 Background: Anticipating clinical benefit early in the treatment course remains a major challenge in oncology clinical research. While standardized measures per RECIST 1.1 are used in randomized clinical trials (RCT) to define treatment response and disease progression, they are not used in clinical care. IPRO (Imaging-based Prognostication)-α is a fully automated, prognostic AI model that generates a survival prediction from a thoracic CT scan. By generating IPRO-α scores at baseline (BL) and on-treatment visits, changes in a patient's prognosis can be quantified. We assessed whether the magnitude of % change from BL (CFB) IPRO-α, reflecting the depth of IPRO-α response, correlates with OS. Methods: IPRO-α was evaluated in an external real-world dataset of 85 aNSCLC patients treated with 1L pembrolizumab monotherapy at 17 cancer centers, who had a BL and week 8 (± 4 weeks) scan after 1L treatment initiation. We divided the cohort into 3 IPRO-α response groups based on % CFB: 1) no response (≤ 0%), 2) intermediate response (0-40%) and 3) high response ( &gt; 40%), to evaluate the association between the magnitude of IPRO-α response and OS. After landmarking at the week 8 CT scan, Kaplan-Meier (KM) and Cox proportional hazard analyses were performed to evaluate the OS benefit for the intermediate and high response groups over the no response group. Results: The median age of the cohort was 68 (IQR 62-75), and 42.3% (n = 36) were males. The median OS of the cohort was 20.4 months (95% CI: 10.5-28.3 months). At week 8, 22 (25.9%) patients had intermediate IPRO-α response, while 8 patients (9.4%) had high response. The median OS of patients with no response was 10.5 months (95% CI: 9.1-23.7 months), compared to 27.0 months (95% CI: 13.3-60.6 months) with intermediate response, and 50.8 months (95% CI: 14.6-not reached) for high response. The HR for intermediate response relative to no response was 0.57 (0.32-1.00, p = 0.05) and for high response was 0.36 (0.15-0.90, p = 0.029). Conclusions: These findings suggest that early IPRO-α response is associated with OS benefit, where greater improvements in IPRO-α were associated with progressively longer OS. This supports the potential of IPRO-α response as an outcome measure and early endpoint in this patient population. Future work will focus on validation in RCTs and comparisons to RECIST-based surrogate endpoints.