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Adjuvant endocrine therapy omission in ER-positive breast cancer treated with neoadjuvant chemotherapy.

525 Background: Adjuvant endocrine therapy (ET) decreases breast cancer (BC) recurrence and improves overall survival (OS) for patients (pts) with estrogen receptor positive (ER+) BC. Omission of adjuvant ET and nonadherence are major issues contributing to worse clinical outcomes. Recent data suggest that the number of pts who omit adjuvant ET may be increasing in Europe [1]. These data have yet to be evaluated in the U.S. We previously reported data from the National Cancer Database (NCDB) that ET omission was more likely in pts with ER+/HER2+ disease who achieved a pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) [2]. Herein we report an updated analysis with a larger cohort designed to examine trends in ET omission over time and the impact on OS in a group of pts at high risk of recurrence. Methods: The NCDB was queried from 2010-2022 for pts with stage I-III ER+BC treated with NAC and surgery. pCR was defined as ypT0, ypN0. Use of adjuvant ET and the impact of adjuvant ET omission on OS in pts with and without pCR were assessed separately based on HER2 status. Adjuvant ET initiation by 1 year was summarized using the cumulative incidence estimate to account for the competing risk of death. OS was analyzed with ET as a time-dependent covariate using multivariable Cox proportional hazards regression. Results: We identified 130,438 pts with ER+BC (78,778 ER+/HER2-, 51,660 ER+/HER2+) who received NAC. Median follow-up was 5 years. Overall, pCR was achieved in 10.0% of ER+/HER2- and 35.9% of ER+/HER2+. On multivariable analysis, ET omission was significantly associated with worse OS in pts with residual disease (RD) [ER+/HER2- (HR 1.80 p<0.001) ER+/HER2+ (HR 1.66 p<0.001] and in those with a pCR [ER+/HER2- (HR 1.38 p=0.002) ER+/HER2+ (HR 1.42 p<0.001)]. Between 2010-2017, adjuvant ET omission was stable, with approximately 10.0% of pts not having initiated ET by 1 year after surgery. The proportion of pts omitting ET overall increased thereafter to 12.9% in 2018, rising to 24.4% in 2022. A sharp increase in ET omission was observed 2021-2022 in ER+/HER2- BC who achieved pCR, with 42.4% omitting ET compared to 25.1% for 2018-2020 and 18.8% for 2010-2017 (p<0.001). Adjuvant ET omission showed more modest but significant increases for other subgroups (p<0.001): ER+/HER2- with RD (8.5% 2010-2017, 12.3% 2018-2020, 18.7% 2021-2022), ER+/HER2+ with pCR (15.1% 2010-2017, 14.0% 2018-2020, 24.4% 2021-2022), and ER+/HER2+ with RD (9.5% 2010-2017, 12.5% 2018-2020, 22.2% 2021-2022). Conclusions: In ER+BC treated with NAC, omission of ET is increasing over time and associated with a higher risk of death, regardless of HER2, RD, or pCR status. These findings have substantial public health implications as they may result in a reversal of the 4-decade improvements in breast cancer mortality. Additional intervention is critical to improve adherence to guidelines. [1] Verreck et al. Breast 2025 [2] Choong et al. SABCS 2022.

Treatment patterns and PD-L1 testing among persistent, recurrent, or metastatic cervical cancer patients in the United States community oncology setting.

5522 Background: Pembrolizumab was approved for persistent, recurrent, or metastatic cervical cancer (PRM-CC) among patients (pts) with PD-L1 expression in October 2021. This followed its June 2018 approval for PD-L1-positive recurrent, metastatic pts who progressed after chemotherapy. This real-world study aimed to describe treatment patterns and PD-L1 testing patterns among pts with PRM-CC between 2018-2024. Methods: Electronic medical record data from The US Oncology Network identified adult PRM-CC pts diagnosed between July 2018 and July 2022 and followed through June 2024. Persistent disease was defined as either absence of a complete response or provider-documented progression within 90 days following the completion of initial CC-related treatment. Results: There were 216 PRM-CC pts eligible for the study. Overall, median age was 55 years and median duration of follow-up was 12.8 months. Overall, 56% (n = 121) of PRM-CC pts had documented PD-L1 testing during the study observation period, of which 78% (n = 94) had a positive result and 7% (n = 8) had undocumented result. Among PD-L1 positive pts without metastatic disease at initial diagnosis (n = 121), 41% were tested after PRM-CC diagnosis date and had a median time from diagnosis to PD-L1 testing of 1.4 months, and 11% were tested prior to PRM-CC diagnosis date. PD-L1 testing increased from 54% to 69% after October 2021, yet 43% of PD-L1+ patients did not receive pembrolizumab after 2021. 12% (8/69) of pts who received pembrolizumab did not have documented PD-L1 testing. Pembrolizumab was received by 27 pts in 1L (pre-2021: 16, post-2021: 11) and 26 patients in 2L pre-2021: 17, post-2021: 9). Most patients had metastatic disease (74%, n = 159), of which 60% (n = 95) presented with metastatic disease at initial diagnosis. Concurrent chemoradiation prior to metastatic disease was received by 38% (n = 81) of pts. The majority of pts with metastatic disease received first line (1L) treatment (n = 86%, n = 137) and 28% (N = 45) of pts initiated 2L treatment. During the first regimen of 1L, 96 pts received a platinum+taxane-containing regimen (+bevacizumab, n = 72). Conclusions: Between 2018-2024, many PRM-CC pts were not tested for PD-L1 although biomarker-driven treatments were available. Among those tested, almost half of PD-L1 positive patients did not receive standard-of-care therapy. The current treatment landscape provides a valuable opportunity to standardize and enhance PD-L1 testing in order to optimize treatment selection and support personalized care in this population. Overall Pembrolizumab initiation-Yes Pembrolizumab initiation-No PD-L1 Testing 216 69 147 Tested, N(%) 121 (56.0) 61 (88.4) 60 (40.8) Positive 94 (77.7) 52 (85.2) 42 (70.0) Negative 19 (15.7) 4 (6.6) 15 (25.0) No result 8 (6.6) 5 (8.2) 3 (5.0) Not Tested, N (%) 95 (44.0) 8 (11.6) 87 (59.2)

Clinically significant immune-related adverse events with perioperative pembrolizumab in early triple-negative breast cancer: Analysis of trial and real-world evidence.

e12652 Background: Pembrolizumab plus chemotherapy improves pathologic complete response (pCR) and survival in early-stage triple-negative breast cancer (TNBC) but can cause immune-related adverse events (irAEs). TNBC-specific real-world toxicity data are limited. We quantified irAE incidence and management impact. Methods: PRISMA-guided systematic review of stage I–III TNBC treated with peri-operative pembrolizumab (neoadjuvant ± adjuvant). Nine studies (phase II–III trials and observational cohorts; N≈2,000) met inclusion. Random-effects meta-analysis pooled proportions for any-grade irAEs, grade ≥3 irAEs, organ-specific irAEs (endocrine, GI/pulmonary, hepatic), and pCR. Heterogeneity was assessed with I². Permanent discontinuation due to irAEs and systemic steroid use were pooled when available; hospitalization, persistence, time-to-onset, and rechallenge outcomes were summarized descriptively when not poolable. Results: Pooled any-grade irAEs were 34% (95% CI 29–43) and grade ≥3 irAEs 12% (95% CI 10–15). Endocrine irAEs (predominantly thyroid dysfunction) occurred in 9.18% (95% CI 5–21). GI/pulmonary irAEs occurred in 4.07% (95% CI 3–5) and hepatitis occurred in 5.12% (95% CI 2–13). Pooled pCR was 64% (95% CI 54–72). Permanent discontinuation due to irAEs was 14.26% (95% CI 10–17), and systemic steroids were required in approximately 16.84% (driven by two real-world cohorts). In single cohorts, hospitalization for grade ≥3 irAEs was 11.4% and rechallenge success 53%. Across studies, irAE occurrence and steroid use were not consistently associated with pCR. Conclusions: Perioperative pembrolizumab yields high pCR in early TNBC, with severe irAEs in approximately 1 in 8 patients. Endocrine events are most common and may be persistent. Clinically meaningful toxicity is frequent: 14.26% discontinue pembrolizumab due to irAEs and 16.84% require systemic steroids. Standardized reporting of management outcomes will refine benefit–risk assessment. Key pooled endpoints (random-effects meta-analysis) and management outcomes (pooled when feasible). Endpoint Estimate Any-grade irAEs 34% (95% CI 29–43) Grade ≥3 irAEs 12% (95% CI 10–15) Endocrine irAEs 9.18% (95% CI 5–21) GI/pulmonary irAEs 4.07% (95% CI 3–5) Hepatitis 5.12% (95% CI 2–13) pCR 64% (95% CI 54–72) Permanent discontinuation (irAE) 14.26% (95% CI 10–17) Systemic steroids for irAEs 16.84% (2 cohorts; not pooled) Hospitalization for grade ≥3 irAEs 11.4% (1 cohort; not pooled) Rechallenge success 53% (1 cohort; not pooled)

Maintenance treatment with toripalimab and anlotinib after anthracycline-based chemotherapy in patients with advanced soft tissue sarcoma (TORANS): A single-arm, phase 2 trial.

11512 Background: To date, there is no established maintenance strategy for patients with advanced soft tissue sarcoma (STS) who achieve disease control following first-line anthracycline-based chemotherapy. Maintenance therapy is therefore under active investigation in this setting. This study assessed the efficacy and safety of toripalimab (a humanized anti-PD-1 monoclonal antibody) combined with anlotinib (a multitargeted tyrosine kinase inhibitor) as a maintenance treatment. Methods: Patients with advanced STS who achieved stable disease or a partial response after at least four cycles of first-line anthracycline-based chemotherapy were enrolled in this single-arm, phase 2 trial and received maintenance therapy with toripalimab (240 mg intravenously on day 1) and anlotinib (12 mg orally once daily on days 1–14) in 21-day cycles. The primary endpoint was the 24-week progression-free survival rate (PFSR 24w ), defined as the proportion of patients who remained free from disease progression through 24 weeks after initiation of maintenance therapy. Secondary endpoints included median progression-free survival (PFS), median overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety. Results: Between April 2022 and May 2025, a total of 52 patients were enrolled; one patient diagnosed with pathologically confirmed metaplastic carcinoma was excluded. As of December 26, 2025, the median follow-up duration was 20 months. The PFSR 24w was 74.5%. The median PFS was 12 months, and the median OS was not reached at the time of data cutoff. Durable partial responses were observed in patients with dedifferentiated liposarcoma (5/14), leiomyosarcoma (2/11), epithelioid sarcoma (2/4), myxofibrosarcoma (1/3), synovial sarcoma (1/3), and pleomorphic rhabdomyosarcoma (1/1), resulting in an ORR of 23.5%. The most common grade 3–4 adverse events were hypertension (n = 10), increased gamma-glutamyltransferase (n = 5), hand-foot skin reaction (n = 3), and hypertriglyceridemia (n = 3). No new safety signals emerged during the course of the trial. Conclusions: Toripalimab in combination with anlotinib as maintenance therapy demonstrated promising efficacy and a manageable safety profile in patients with advanced STS following first-line anthracycline-based chemotherapy. Clinical trial information: ChiCTR2100054901.

Gender-based differences in malnutrition among patients with stage IV lung adenocarcinoma.

e22669 Background: Malnutrition, cachexia and weight loss are potential complications in patients with advanced lung cancer and are associated with worse clinical outcomes. Data evaluating sex-based differences in malnutrition among patients with metastatic lung adenocarcinoma remain limited. Methods: We conducted a retrospective cohort study using the TriNetX Global Collaborative Network, that includes 172 healthcare organizations in the United States of America. Adults with age 18–90 years with Stage IV lung adenocarcinoma were identified. Cohort A included females (n=1,075) and Cohort B included males (n=1,128). Malnutrition was defined by ICD-10 codes for malnutrition (E40–E46), cachexia (R64), or abnormal weight loss (R63.4) occurring within 365 days of diagnosis. Patients with malnutrition prior to the index event were excluded. Propensity score matching (1:1) was performed for age, race/ethnicity, and comorbidities that included nicotine dependence, heart failure, diabetes mellitus, overweight/obesity, disorders of the thyroid gland, alcohol use disorder and nicotine use disorder. Risk-based outcomes were compared between cohorts. Results: After propensity score matching, 877 patients remained in each cohort. Within one year of diagnosis, malnutrition occurred in 8.1% of females (67/832) and 11.6% of males (94/812). Female sex was associated with a significantly lower risk of malnutrition compared with males (risk difference −3.5%, 95% CI −6.4 to −0.6; p=0.016). The risk ratio was 0.70 (95% CI 0.52–0.94), and the odds ratio was 0.67 (95% CI 0.48–0.93). Conclusions: In this multicenter cohort of patients with Stage IV lung adenocarcinoma, males experienced a significantly higher risk of malnutrition within one year of diagnosis compared with females. These findings support the need for careful nutritional screening and targeted interventions, particularly among male patients with advanced lung cancer.

Age and the genomic landscape of AML in precision oncology: An analysis using ASH HematOmics Program.

6543 Background: Age is a major determinant of prognosis and treatment selection in acute myeloid leukemia (AML), yet the extent to which chronological age reflects underlying genomic and transcriptomic features remains incompletely characterized. The American Society of Hematology HematOmics Program (ASHOP) provides a centralized, clinically annotated genomic resource enabling systematic evaluation of age-associated AML biology across molecular subtypes. Methods: We conducted a cross-sectional analysis of adults with AML using ASHOP data. Patients were categorized by age (<40, 40-59, 60-74, and ≥75 years). AML molecular subtypes were defined based on recurrent cytogenetic and genomic alterations (NPM1, PML::RARA, CBFB::MYH11, MECOM, CEBPA, AML-MR, KMT2A, DEK::NUP214, TP53, and other recurrent translocations), aligned with WHO classification. Adverse genomic risk was defined by AML-MR, MECOM, and TP53. Gene expression levels for epigenetic regulators (DNMT3A, TET2, IDH1, IDH2, FLT3) and stemness-associated genes (HOXA9, MEIS1, HLF, GATA2, PROM1) were standardized as z-scores, and composite scores generated. Associations were assessed using chi-square tests, linear regression, and multivariable models adjusted for sex. Results: Among 302 patients (mean age 71.1 ± 17.3 years; 47.7% aged ≥75; 54.3% male), the most common subtypes were NPM1 (20.5%), PML::RARA (16.6%), CBFB::MYH11 (15.6%), MECOM (14.2%), CEBPA (10.9%), AML-MR (9.6%), and KMT2A (7.6%). Subtype distribution varied modestly across age groups (p=0.053) but not by sex (p=0.858). Adverse genomic risk increased significantly with age (p=0.016). In multivariable logistic regression adjusted for sex, patients aged ≥75 had significantly higher odds of adverse genomic features (OR 2.78, 95% CI 1.26, 6.12; p=0.011), while sex was not independently associated (p=0.325). In transcriptomic analyses (n=265), age was not associated with individual epigenetic or stemness genes, with age and sex explaining minimal variance in composite scores (epigenetic score R²=0.013, p=0.506; stemness score R²=0.003, p=0.957). In contrast, molecular subtype showed strong associations. Subtype along with age and sex explained 16.4% of epigenetic score variance (R²=0.164; p<0.001) and 38.0% of the stemness score variance (R²=0.380; p<0.001). Key stemness genes were highly subtype-dependent (HOXA9 R²=0.709; MEIS1 R²=0.599; both p<0.001), driven primarily by NPM1 and KMT2A subtypes. Conclusions: Advanced age in AML is associated with adverse genomic risk accumulation but explains minimal variance in stemness or epigenetic transcriptional programs. Instead, these programs are largely determined by molecular subtype. Hence, stemness and epigenetic programs are intrinsic properties of AML molecular subtypes rather than age, supporting subtype-driven risk stratification and therapeutic decision-making in the precision oncology era.

Management of amivantamab-associated scalp toxicity: A multicenter retrospective cohort study.

e24207 Background: Scalp toxicities, namely erosive pustular dermatosis (EPD) and scalp folliculitis, are common and often challenging toxicities associated with amivantamab, a bispecific epidermal growth factor receptor / mesenchymal-epithelial transition (EGFR/MET) antibody for EGFR-mutant non-small cell lung cancer (NSCLC). While prophylactic strategies for preventing scalp toxicity have been identified in the COCOON study (oral tetracyclines, topical clindamycin, ceramide-based moisturization, and sun-protection), data on real-world management outcomes for this toxicity remain limited. Methods: We retrospectively identified patients with amivantamab-induced scalp toxicity at two tertiary academic centers from 5/2022-11/2025. Severity was graded with Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Clinical response was categorized as complete resolution, partial improvement, or no improvement. Results: Of 74 patients prescribed amivantamab, 15 patients had amivantamab-induced scalp toxicity. EPD was the predominant phenotype (12/15; 80%). Baseline severity was Grade 2 (9/15; 60%) or Grade 3 (5/15; 33.3%). In our cohort, 14/15 (93.3%) experienced clinical improvement with multimodal management, most commonly including high-potency topical corticosteroids (14/15; 93.3%), oral doxycycline (14/15; 93.3%), topical clindamycin (9/15; 60%), and oral retinoids (3/15; 20%). In three refractory cases, adding oral retinoids (isotretinoin or acitretin) to the initial regimen (with discontinuation of oral tetracycline), achieved partial improvement in two and complete clearance in one. Complete scalp toxicity clearance (Grade 0) was achieved in 8/15 (53.3%), particularly 2/5 (40%) patients with Grade 3 toxicity (3-grade improvement) and 6/9 (66.7%) with Grade 2 toxicity (2-grade improvement). Median time to complete resolution among patients with Grade 2 scalp toxicity was 77 days (range 75-96). Among patients achieving complete resolution (n = 8), 4 (50%) received a regimen that included high-potency topical corticosteroids, doxycycline, and topical clindamycin. While amivantamab dose modifications were required in 9/15 (60%) for cutaneous toxicities, all patients continued therapy. Conclusions: Scalp toxicities represent a frequent dose-limiting toxicity with amivantamab. Our study shows scalp toxicities with amivantamab are generally responsive to therapy comprising oral doxycycline, topical corticosteroids, and topical antibiotics. For refractory cases, escalation to oral retinoids demonstrated additional improvement, suggesting oral retinoids are a promising option for severe scalp toxicity. Study limitations include retrospective nature and small sample size. Our findings extend the prevention-focused COCOON data by providing outcomes-based evidence for strategies for managing scalp toxicities arising on amivantamab therapy.

Debriefing initiative on the oncology firm.

e21001 Background: Medical oncology is a core internal medicine residency rotation at Yale New Haven Hospital (YNHH). In addition to providing medically complex care, residents support patients facing significant psychosocial distress, challenging palliative needs, and end-of-life care. Furthermore, research suggests that trainees rotating on an inpatient hematology-oncology ward rotation may have subsequent decreased interest in the field, while increased empathy and resilience may be associated with maintaining or improving interest in medical oncology (McFarland et al. 2015). Thus, we implemented formal debriefing sessions for residents on the oncology rotation with the goal of decreasing emotional burden and improving trainee satisfaction. Methods: Formal IRB approval was obtained. A reflection and debriefing session was designed and scheduled for the end of each oncology rotation. Sessions were led by a senior resident, oncology fellow, or medical oncology attending leader. Participants (residents on the oncology service at YNHH) filled out pre- and post-surveys that posed questions in the form of Likert scales that assessed resident perception of burnout, current support, value of debriefing, and comfort in conducting debriefing. The pre- and post-surveys were compared using Fisher-Freeman-Halton exact test (alpha = 0.05) to look for differences in responses between pre- and post-intervention. Results: 60% of residents surveyed (N=20) stated that work left them emotionally drained. While 90-95% of residents answered that debriefing is essential for team member well-being, when residents were asked about their personal experience, on average only 33% of critical incidents were followed by a debriefing session. Post-intervention, participants who denied “feeling alone in processing emotionally challenging patient care experiences” rose from 30% to 55%. Those who answered “strongly agree” or “agree” to the question of feeling confident in initiating a debriefing session rose from 70% to 90% post intervention, while confidence in leading a debriefing session rose from 60% to 80%. 85% of residents felt like the debriefing session helped them process recent difficult patient care experiences. Conclusions: While no significant differences in pre- and post-surveys were found, likely partly due to sample size, the data above suggests that residents experience significant emotional challenges during their oncology rotation while also experiencing a gap in current support following critical incidents. Meanwhile, debriefing sessions were shown to be well-received overall and emotionally supportive for residents. Finally, residents increased in comfort in using debriefing skills in the future, making this intervention a solid investment in future well-being at work. We are hopeful that the continuation of the project will result in more conclusive data in support of this initiative.

Bridging multi-omics to routine precision oncology: Biologically informed knowledge transfer for precision pCR prediction in neoadjuvant immunotherapy.

e12569 Background: Immune Checkpoint Inhibitors (ICI) significantly improve pCR rates, yet optimal patient selection is impeded, particularly in resource-limited settings, by reliance on costly omics data unavailable in standard practice. To develop the iM-KT (immune Multi-modal Knowledge Transfer) framework, a biologically informed model designed to distill complex immune landscapes into accessible routine data, enabling precise pCR prediction relying solely on accessible routine inputs, achieving robust predictive performance without the need for costly omics profiling. Material and. Methods: iM-KT was pre-trained on the I-SPY 2 landscape (n = 979), integrating transcriptomic, proteomic, MRI, and clinical data. We employed a cross-modal knowledge transfer paradigm to distill high-dimensional omics insights into standard inputs (MRI, clinical factors). Specifically, a Teacher network, trained on matched multi-omics, supervised a Student network restricted to MRI and clinical variables (age, HER2, HR). To ensure biological alignment, the Student was optimized to reconstruct immune-pathway gene expression. The pCR predictor was then trained on the NACT+ICI subset (n = 69) and validated in an independent real-world cohort (n = 59). Performance endpoints included pCR accuracy, Distant Recurrence-Free Survival (DRFS), and biological validation via Gene Set Enrichment Analysis (GSEA). Results: In the independent test cohort receiving NACT+ICI, iM-KT outperformed receptor status in predicting pCR (AUC 0.76 vs. 0.65, p = .004). Prognostically, iM-KT effectively stratified risk, distinguishing predicted responders from non-responders with significant separation (HR 0.18; 95% CI, 0.04-0.88; p = .034). Within the surgical non-pCR subpopulation (n = 27), the model distinguished a favorable "near-pCR" subset with a clinically relevant reduction in recurrence risk (HR 0.34, recurrence 16.7% vs. 33.3%), implying the potential to de-escalate adjuvant therapy for biologically responsive patients. Biological validation confirmed predictions were underpinned by Primary immunodeficiency (NES = 2.70; p < .001) and Th1/Th2 cell differentiation (NES = 2.69; p < .001), capturing complex immune dynamics that standard receptor status fails to resolve. Conclusions: iM-KT demonstrates that accurate response prediction is achievable in clinical practice without relying on high-cost omics data. By successfully transferring intrinsic immune mechanisms into routine diagnostics, the framework captures subtle biological responses missed by standard pathology, offering a scalable strategy to guide personalized therapeutic escalation or de-escalation in the neoadjuvant immunotherapy setting.

Age and frailty analyses of transplant-ineligible (TIE) patients (pts) with newly diagnosed multiple myeloma (NDMM) in the phase 3 MAIA and CEPHEUS trials of daratumumab + lenalidomide-dexamethasone (Rd) and bortezomib-Rd (VRd).

7569 Background: MAIA and CEPHEUS trials demonstrated that daratumumab (Dara) with standard of care (SOC) VRd or Rd significantly improved clinical outcomes versus SOC in TIE NDMM. Here we describe efficacy and safety in TIE pts from both trials by age and baseline (BL) frailty using the latest data cuts. Methods: Pts were randomized 1:1 to DRd (n=368) or Rd (n=369) in MAIA and 1:1 to DVRd (n=144) or VRd (n=145) in CEPHEUS. Progression-free survival (PFS), complete response or better (≥CR), overall MRD negativity (neg) at 10 -5 with ≥CR, sustained MRD neg with ≥CR (confirmed MRD neg ≥12 ± 1 months [mo] apart without MRD positivity in between), and safety were assessed by age (<70, 70–<75, or ≥75 years [y]) and BL frailty (assessed by IFM simplified frailty score: 0–1, non-frail; ≥2, frail). Results: Median follow-up was 64.5 mo in MAIA and 76.0 mo in CEPHEUS. In MAIA, 155 (21%) pts were <70 y, 261 (35%) 70–<75 y, and 321 (44%) ≥75 y; 341 (46%) pts were frail, 88.0 % of whom were ≥70 y. In CEPHEUS TIE pts, 70 (24%) pts were <70 y, 133 (46%) 70–<75 y, and 86 (30%) ≥75 y; 83 (29%) pts were frail, 86% of whom were ≥70 y. DRd or DVRd improved PFS, MRD neg rates, sustained MRD neg rates, and ≥CR rates vs Rd or VRd arms across age and frailty subgroups in both trials (Table). Safety was consistent with established individual drug profiles, and adverse event rates were generally comparable across treatment arms and subgroups within both trials. Additional data on patient-specific factors relevant to these subgroups will be presented. Conclusions: Dara-based regimens improved efficacy outcomes across subgroups in MAIA and CEPHEUS trials, reinforcing Dara-based regimens as SOC in TIE NDMM regardless of age or frailty. These data offer clinically relevant insights to help guide treatment selection for TIE pts. Clinical trial information: NCT03652064 ; NCT02252172 . PFS, hazard ratio (95% CI) ≥CR rate, % MRD neg with ≥CR (10 -5 ) rate, % Sustained MRD neg with ≥CR (10 -5 ) rate, % Age/ Frailty status MAIA* CEPHEUS** MAIA* CEPHEUS ** MAIA* CEPHEUS** MAIA* CEPHEUS ** <70 y 0.35 (0.21–0.56) 0.60 (0.31–1.18) 56.4 vs 31.2 85.7 vs 68.6 35.9 vs 11.7 74.3 vs 42.9 25.6 vs 3.9 62.9 vs 28.6 70–<75 y 0.64 (0.45–0.89) 0.60 (0.37–0.99) 56.2 vs 31.3 77.9 vs 69.2 36.2 vs 12.2 55.9 vs 47.7 20.8 vs 5.3 45.6 vs 38.5 ≥75 y 0.59 (0.44–0.79) 0.46 (0.22–0.94) 44.4 vs 28.6 80.5 vs 44.4 26.9 vs 9.9 58.5 vs 26.7 13.8 vs 3.1 43.9 vs 15.6 Frail 0.64 (0.48–0.85) 0.62 (0.32–1.18) 44.8 vs 33.1 72.9 vs 54.3 25.6 vs 13.0 56.3 vs 34.3 15.7 vs 4.1 39.6 vs 17.1 Non-frail 0.48 (0.36–0.64) 0.51 (0.34–0.78) 56.6 vs 27.5 84.4 vs 63.6 37.8 vs 9.5 63.5 vs 41.8 21.4 vs 4.0 54.2 vs 32.7 *MAIA: DRd vs Rd; **CEPHEUS: DVRd vs VRd.

Comparing induction strategies in acute myeloid leukemia: 10-year real-world experience with 7+3 and HMA/venetoclax.

6524 Background: Hypomethylating agents (HMA) combined with venetoclax are the standard of care for AML in adults ineligible for intensive chemotherapy, but use is expanding to fit patients given prospective data suggesting comparable outcomes. Whether these findings are reproducible in real-world practice remains under investigation. Methods: We conducted a retrospective cohort study of adults with newly diagnosed AML treated at the University of Kentucky from 2016-2025 with either 7+3 or HMA/venetoclax. Overlap propensity score weighting balanced age, sex, ECOG, ELN risk group, prior MDS, and therapy-related AML. Primary endpoints were CR/CRi, RFS, OS, and 30-day mortality. Cox models included allogeneic HSCT as a time-varying covariate. Survival outcomes were stratified by ELN risk group and mutational risk group according to venetoclax sensitivity (favorable: NPM1 and IDH1/2 , adverse: TP53 and FLT3 ). Results: Prior to weighting, patients treated with HMA/venetoclax were older (68 vs. 50 years), had worse performance status (mean ECOG 1.2 vs. 0.7), and were more likely to have prior MDS, therapy-related AML, and less favorable ELN risk. Unweighted data demonstrated a median OS of 13.3 months for HMA/venetoclax and 19.6 months for 7+3. After overlap weighting of 379 patients (250 received 7+3 and 129 received HMA/venetoclax), acceptable covariate balance was achieved with all standardized differences < 0.01. HMA/venetoclax was associated with numerically higher odds of achieving CR/CRi compared with 7+3 (OR 1.84, p=0.09), and this reached significance in adverse-risk disease (OR 2.31, p=0.006). 30-day mortality was similar between 7+3 and HMA/venetoclax groups (8.3% vs. 8.0%, p=0.96). Among patients who achieved CR/CRi, no significant difference in relapse was noted (p=0.24). RFS and OS did not differ significantly between treatment groups (p=0.76 and 0.18, respectively). Analysis of ELN risk subgroups and mutation subgroups incorporating venetoclax sensitivity demonstrated no association with treatment group in survival outcomes (for OS, p=0.53 and 0.43, respectively), suggesting no effect modification from these variables. Allogeneic HSCT was strongly associated with improved OS (HR 0.26, p<0.001), which persisted after adjusting for ELN risk (HR 0.39, p<0.001) and mutational subgroups (HR 0.44, p=0.001). Across all models, treatment assignment did not significantly impact OS once transplant was modeled as a time-dependent variable. Conclusions: After accounting for baseline confounding and allogeneic HSCT as a time-varying covariate, survival in AML is primarily driven by molecular risk profile and transplant rather than initial induction strategy. These results support further investigation of HMA/venetoclax as a frontline alternative in fit patients with AML and the intention to proceed to transplant.

A pragmatic, hybrid observational study evaluating the effectiveness of trastuzumab deruxtecan (T-DXd) in patients with human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC) 3+ solid tumors: DESTINY-PanTumor04.

TPS11202 Background: Patients with advanced or metastatic HER2 IHC 3+ solid tumors have limited treatment options beyond first-line settings, with generally poor outcomes. T-DXd is a HER2-directed antibody-drug conjugate approved in multiple countries, including in the US for patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumors who have received prior treatment and have no satisfactory alternative therapies. Building on existing clinical trial data, DESTINY-PanTumor04 evaluates the real-world effectiveness of T-DXd in HER2-positive (IHC 3+) solid tumors, using a hybrid data collection approach that enhances efficiency for sites and physicians and facilitates study implementation. Methods: DESTINY-PanTumor04 (NCT07124000) is a multicenter, pragmatic observational, real-world study evaluating the effectiveness of T-DXd (5.4 mg/kg IV Q3W) in adult patients in the US with previously treated, locally advanced, unresectable, or metastatic HER2-positive (IHC 3+ by local testing) solid tumors. Data collection will use a hybrid approach, combining primary data collection of baseline tumor burden, comorbidities, ECOG status, treatment response, and survival, with secondary data collection from electronic health record (EHR) abstraction for all other data. Approximately 100 patients will be enrolled across US sites, including community oncology practices and academic medical centers within an existing US oncology network from Paradigm Health. Participating sites will use technological resources that support the identification of eligible patients and enable efficient EHR-to-electronic data capture and transfer, minimizing physician time while improving compliance in data completeness and accuracy. Eligible patients must have disease progression following ≥1 prior systemic treatment for metastatic or advanced disease, have no alternative treatment options, and have a clinical decision for T-DXd treatment in accordance with the FDA label. Patients with breast cancer, colorectal cancer, non-small cell lung cancer, gastric or gastroesophageal junction cancers, or hematologic malignancies will be excluded. Primary endpoints are real-world objective response rate, defined as the proportion of patients with a complete response (CR) or partial response (PR) as determined by clinician assessment per criteria used in routine clinical practice; and real-world duration of response, defined as the time from first objective response (CR or PR) to disease progression as determined by clinician assessment per criteria used in routine clinical practice, or death. Secondary endpoints include real-world time to treatment discontinuation and real-world time to next treatment. Enrollment began in September 2025 and is ongoing. Clinical trial information: NCT07124000 .

Phase I study of zeaxanthin alone or in combination with pembrolizumab in metastatic solid tumors.

TPS2696 Background: Zeaxanthin is a carotinoid synthesized by plants that accumulates via dietary intake in the macula. Preclinical studies demonstrated anti-proliferative properties in cancer cell lines in vitro. In uveal melanoma cell lines SP6.5 and C918, zeaxanthin reduced cell viability in a dose dependent manner while not doing so in normal ocular melanocytes. Decreased cell viability associated with decreased expression of anti-apoptotic proteins bcl-2 and bcl-xL and increased expression of pro-apoptotic bak and bax (1). Anti-proliferative effects were demonstrated in nude mice inoculated in the choroid with uveal melanoma cells (2). Zeaxanthin enhances anti-tumor immunity. Screening a blood nutrient compound library found zeaxanthin to augment CD8+ T-cell activity through direct engagement with the T-cell receptor (3). Murine models showed zeaxanthin enhanced anti-cancer efficacy of anti-PD-1 immunotherapy (3). Pro-apoptotic and immunomodulatory properties of zeaxanthin suggest potential for efficacy in treating cancer patients warranting clinical investigation. The primary objectives of this phase I study are to determine safety and tolerability of escalating doses of zeaxanthin monotherapy or combination of zeaxanthin plus pembrolizumab in patients with metastatic solid tumor malignancies and to determine MTD and recommended phase 2 dose. Secondary objectives assess pharmacokinetics and efficacy. Exploratory endpoints assess blood based biomarkers, transcriptome changes, and immunologic effects. Pre- and on-treatment tumor biopsies assess tumor microenvironment change. Methods: This 2 cohort study treats standard therapy refractory metastatic solid tumor patients with zeaxanthin (monotherapy cohort) or zeaxanthin and pembrolizumab (combination cohort). Combination cohort inclusion requires prior progression on a PD-1/L1 inhibitor. Oral zeaxanthin is administered daily with escalating doses (2 mg/kg to 10 mg/kg). The combination cohort escalates doses of zeaxanthin with a fixed dose of pembrolizumab (400 mg) infused every 6 weeks. Dose escalation utilizes a 3+3 design. Combination cohort dose level enrollment occurs after a zeaxanthin dose demonstrates no monotherapy DLT. Pharmacokinetic assessments occur at specified time points, Required large volume blood draws for pharmacodynamic analysis and optional tumor biopsies are obtained within 15 days prior to treatment initiation and at 6 weeks on treatment. Cohort 1 of zeaxanthin monotherapy (2 mg/kg daily) completed without DLT. Enrollment to monotherapy cohort 2 (zeaxanthin 4 mg/kg daily) and combination cohort 1 (zeaxanthin 2 mg/kg plus pembrolizumab 400 mg IV every 6 weeks) began November 2025 and are actively accruing patients. Clinical trial registry number: NCT05232409. (1) Bi et al. Evid. Based Compl. Alt. Med. (2013)12; (2) Xu et al. J Opthal (2015)10; (3) Zhang et.al. Cell Rep. Med. (2025)6. Clinical trial information: NCT05232409 .

Racial differences in survival and prognostic factors among patients with mycosis fungoides and Sézary syndrome: A systematic review and meta-analysis.

e19112 Background: Mycosis Fungoides (MF) and its leukemic variant, Sezary Syndrome (SS), are the most common forms of cutaneous T-cell lymphoma. Racial differences in survival outcomes between white and black patients are contradictory between studies. Objective: To evaluate the survival outcomes among white and black patients with MF and to determine other prognostic factors of the disease. Methods: A systematic search of PubMed, Scopus, and Web of Science was conducted from inception through May 2025 to identify studies comparing survival outcomes and prognostic factors between Black and White patients with MF/SS. Review articles, clinical trials, gray literature, and studies not reporting survival outcomes by race were excluded. Meta-analysis was performed using RevMan software. Results: Out of 468 studies, 12 were included in the final analysis, comprising 16514 patients. White patients comprised 65.5%, whereas 16% were black. Black patients were diagnosed at younger ages (MD= -6.69, 95% CI = [-10.12, -3.27], p=0.0001). Black patients are significantly more likely to be diagnosed at higher stages at diagnosis compared to white patients (RR=1.34, 95% CI= [1.01, 2.03], p=0.0008). Also, black patients have worse Overall Survival (OS)compared to white patients (HR= 1.46, 95% CI= [1.33, 1.61], p=0.004) and a higher mortality rate compared to white patients (RR= 2.23, 95% CI= [0.61, 8.92], p=0.0004). Patients with advanced stage have 2.85 times worse survival than other patients (HR=2.85, 95% CI= [2.57, 3.15], p=0.0001) and patients with advanced age at diagnosis (>60 years) have 1.06 times worse OS compared to younger patients (HR= 1.06, 95% CI= [1.06, 1.07], p=0.00001). Advanced age (>60), late stages at diagnosis, erythroderma, and hypopigmented lesions were the most noticeable poor prognostic indicators of OS. Conclusions: Black patients are diagnosed at an earlier age and at later stages than white patients. Additionally, overall survival is significantly worse in black patients compared to white patients. This racial disparity warrants further investigation and correction of medical policies, socioeconomic factors, or biologic differences that may underlie these findings.

Green-synthesized tricalcium silicate nanoparticles from Salvia officinalis for antimicrobial coating of clear aligners and prevention of enamel demineralization

A Circular Manufacturing Platform for High‐Performance Cellulosic Fibers via Hydrogen‐Bond Unzipping and Rezipping

ABSTRACT This study outlines a closed‐loop manufacturing process for cellulosic fibers designed to meet the textile industry's urgent demand for eco‐friendly, cost‐effective solvents, circular‐design principles, and superior material performance. The process utilizes a deep eutectic solvent composed of calcium chloride, formic acid, and water, which effectively facilitates cellulose dissolution and partial esterification. Followed by dry‐jet wet spinning and ethanol‐induced coagulation, the initially disordered cellulose chains are reorganized into an ordered, compact fibrillar structure. The resulting fibers showcase a relative crystallinity of 63.9%, tensile strength of 222 MPa, elongation exceeding 20%, and thermal stability above 180°C. Furthermore, they possess textile‐relevant properties including thermal conductivity of 0.064 W·m −1 ·K −1 , moisture regain of 12.4%, and luster comparable to cuprammonium rayon. Significantly, the process allows for the concurrent recovery of both the solvent and coagulant, maintains fiber reusability, and minimizes waste and costs. The life‐cycle assessment indicates that this approach significantly reduces the carbon footprint and resource depletion compared to conventional rayon production. These findings establish a cost‐effective, eco‐friendly alternative to current solvent systems, addressing both environmental and industrial needs.

New options for platinum-resistant ovarian cancer: Are we in the right direction?

e17566 Background: Ovarian cancer (OC) is the deadliest gynecologic cancer, often diagnosed in advanced stages. Even with combined strategies in the first line that include cytoreduction and systemic treatments, most cases will relapse and become resistant to platinum (PROC). PROC is a clinical unmet need and, until 2025, there was no treatment with overall survival (OS) benefit. MIRASOL, ROSELLA and KEYNOTE-B96 trials have changed this, showing OS benefit. However, these trials’ criteria do not seem to reflect real patients, raising doubts about their feasibility in clinical practice. This study evaluated the applicability of these trials’ criteria in real-world population. Methods: Cross-sectional study of women with high-grade epithelial OC diagnosed between Jan 2016-Dec 2024 (median follow-up 27.8 months [4.0-108.2]) at a comprehensive cancer center. Disease evolution was reviewed, focusing on platinum resistance stage. Cut-off date for the database was Dec 31, 2025. Results: A total of 127 patients were included. At diagnosis, median age was 64 years and the majority did not present BRCA mutations (112, 88.2%), had ECOG-PS ≤2 (119, 93.7%), serous tumors (122, 96.1%) in stage III (65, 51.2%). Twenty-six (20.5%) underwent upfront surgery and 38 (29.9%) achieved complete cytoreduction. All received platinum in first line. Eighteen (14.2%) were primary platinum refractory. In the remaining population (109, 85.8%), median time from diagnosis to platinum resistance was 21.2 months [1.3-82.7]. At PROC timepoint (median follow-up 7.9 months [0.5-76.9]), 90 (82.6%) women had received two prior platinum-based chemotherapy lines [1 line, 40 (36.7%); 2 lines, 50 (45.9%)] and 17 (15.6%) had three lines. Bevacizumab was included up to the third line in 45 (41.3%) patients. In third line, 5 (4.6%) already platinum resistant received paclitaxel monotherapy. Sixteen (14.7%) were unfit for further treatment due to lack of clinical conditions. Per trial criteria, 90 (82.6%) qualified for KEYNOTE-B96 and 45 (41.3%) for ROSELLA; 43 (39.4%) could be accepted for both and 17 (15.6%) for neither. Five (4.6%) patients met MIRASOL clinical criteria — we only had folate receptor alpha (FRα) expression data available in 10; assuming SORAYA high-FRα threshold, 32 (29.4%) would be included. Reviewing these criteria (and excluding patient's comorbidities), tumor histology, primary platinum refractoriness, prior lines of treatment and FRα expression are the main reasons that can rule out a patient — across the entire population (127), 35 (27.6%) would not be eligible. Conclusions: The PROC poor prognosis justifies new therapeutic options. However, despite OS benefit shown in recent trials, a substantial proportion of real-world patients do not meet trials’ criteria and thus cannot benefit from these advances. In future, probably only real-world evidence will address this.

Desmocolin-3–directed immunotherapy in recurrent/metastatic head and neck squamous cell carcinoma.

2503 Background: Recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC) are aggressive tumors. In pre-treated R/M HNSCC observed response rates were 13.0% (nivolumab; CheckMate 141) and 14.6% (pembrolizumab; KEYNOTE- 040), with median PFS 2.0 months and 2.1 months, respectively. Desmocollin3 (DSC3) is a surface protein expressed by HNSCC. DSC3 directed immunotherapy (CADI-05) is useful in DSC3 expressing cancer like Squamous NSCLC, bladder cancer, and melanoma. This study evaluated its efficacy (ORR, PFS, OS) in DSC3 expressing R/MHNSCC. Methods: In this investigator initiated single-arm, study patients with RMHNSCC expressing DSC3 were recruited. Tumor infiltrating lymphocytes (TIL), PD-L1, and P16 were also evaluated. All patients received 0.1ml CADI-05 intradermally + intralesional (for fungating/discharging solid lesions were present) every 4 weeks. Additional treatment was administered as per PI discretion. All patients were followed up until disease progression, or death. Results: Between May 2024 and July 2025, 20 patients were enrolled (males 17, females 3). The mean age was 55 yrs (range 34-87 yrs). Primary sites included tongue 9, buccal mucosa 9. All had undergone two lines of therapy with a mean of 2.55. Of 20 patients, 15 had progressed on prior therapy (6 stage IVC). Baseline mean parameters were mean DSC3 TPS - 41%, (95% CI, 32.67 - 49.33), mean PD-L1 CPS 27 (95% CI,10.61 - 33.39), mean TIL 17% (95% CI ,10.43 - 23.57). All were HPV negative. Additional therapy received included EGFR TKI (15), EGFR mAb (2), oral metronomic therapy (1) and none (2). Disease control rate was 45% (9/20) with overall response rate (ORR) 35% [7/20; 2 CR and 5 PR]. At a median follow-up of 155 days, mean (median) PFS and overall survival were 165 (115) and 197 (155) days, respectively. Mean (median) duration of response was 280 (332) days with 8 patients alive at the last follow up. This is significantly better than achieved with current therapies. Responders had higher DSC3 expression compared to non-responders (mean DSC3 50% vs 29%; p= 0 .002537). ORR was higher in patients with Stage IVA (57% ) compared to IVC (20% ) DSC3 TPS was higher than PD-L1 CPS in all patients with disease control. TIL and PD-L1 levels were not correlated with response. Injection site ulcer was the only side effect seen in 8 (40%), which include 6 (75%) of the responders. No systemic adverse events were observed. Conclusions: DSC3 targeted immunotherapy was safe and improved outcomes in pre-treated R/M HNSCC expressing DSC3, with disease control rate 45%, response rate 35%. Median duration of response was 332 days with median PFS and OS of 115 and 155 days, respectively.

Impact of an audiovisual educational intervention on gastric cancer knowledge and health literacy in a Mexican population.

e22533 Background: Gastric Cancer (GC) remains a major global health burden, with rising incidence among individuals under 50 years of age and markedly poor survival when diagnosed at advanced stages. Despite the critical role of prevention and early detection, structured population-level education or screening strategies for GC are lacking in most Latin American countries. Limited health literacy may contribute to low participation in preventive efforts. This study evaluated the impact of a brief audiovisual educational intervention on GC knowledge in a mexican population and explored sociodemographic predictors of baseline knowledge and learning gain. Methods: This is a quasi-experimental pre-post intervention study among adults without prior GC. Participants completed a validated 18-item knowledge questionnaire before and one month after viewing a short education video and an illustrated brochure addressing GC risk factors, symptoms, heredity and prevention. Total scores ranged from 0-18, internal consistency was assessed using Cronbach’s . Changes in global scores were evaluated using Wilcoxon signed-rank test, and item-level changes with McNemar’s test. Multivariable linear regression models identified demographic predictors of pre-post intervention scores, and knowledge gain ( = post-pre). Results: A total of 400 participants completed both assessments. The mean age was 40.5±16.1 years, only 2.5% had undergone a prior endoscopic study. The intervention produced a significant improvement in knowledge, median score increases from 11 to 15; mean gain was 3.27±2.81 points (Z = 16.21, p < 0.001), with a large effect size (r = 0.81). Seventeen of 18 items (94%) demonstrated significant improvement (p < 0.05), particularly in recognition of GC risk factors, hereditary nature, and preventive practices. The questionnaire showed acceptable reliability (α = 0.738 pre; α = 0.656 post). In regression analyses, years of education and place of residence were independently associated with knowledge outcomes. Higher education was associated with greater post-intervention scores (B = 0.19 per year, p < 0.001) and larger knowledge gains (p < 0.001). Residence in peripheral zones was associated with higher baseline knowledge but smaller learning gains. Post-intervention 11 participants referred having an endoscopic screening procedure done. Conclusions: A brief, low-cost audiovisual education intervention significantly improved gastric cancer knowledge in a Mexican population, with large effect size and broad-item impact. Educational attainment emerged as a key modifier of learning, underscoring the importance of tailoring prevention strategies to health literacy levels. Scalable educational interventions may represent an effective equitable approach to strengthen gastric cancer prevention and early detection in regions lacking structured screening programs.

Sulfidogenic bacteria and the risk of colorectal cancer.

e15727 Background: Dietary patterns rich in specific sulfur-containing foods that can be metabolized into hydrogen sulfide by the gut microbiota have been associated with increased risk of colorectal cancer (CRC). Long-term exposure to dietary derived hydrogen sulfide is capable of damaging the intestinal epithelium and promoting carcinogenesis and has been hypothesized to contribute to recent increases in colorectal adenomas and cancers, particularly in younger adults (age < 50). This study evaluated whether sulfur-metabolizing enzymes are differentially enriched in individuals with CRC and whether these associations vary by age using publicly available human microbiome data. Methods: We performed a two-stage individual patient data meta-analysis (IPDMA) of fecal metagenomic sequencing data from 692 CRC patients and 609 healthy controls across eleven studies. Relative abundances of 52 sulfur-metabolizing enzyme-catalyzed reactions, annotated by Enzyme Commission number, were extracted using HUMAnN3. Logistic and mixed-effects regression models adjusted for age, gender, and BMI were used to evaluate associations between enzyme presence and CRC case status. Species-level contributions to sulfur-metabolizing genes were mapped. Results: Across eleven metagenomic cohorts, several sulfur-metabolizing enzymes, such as sulfolactaldehyde reductase, peptide-methionine sulfoxide reductase, dimethylsulfoxide reductase, were enriched in individuals with CRC. In contrast, enzymes involved in cysteine and methionine synthesis were more common in healthy controls. Age-stratified analyses demonstrated minimal effect modification by younger versus older age groups, indicating that sulfur-metabolizing pathways may be consistently associated with CRC across the age spectrum. Species-level profiling revealed that several bacterial species, including F. nucleatum , I. butyriciproducens , and B. wadsworthia , carried a higher prevalence of sulfur-metabolizing genes in CRC samples. Early-onset CRC samples were enriched for sulfur-metabolizing genes in species such as Citrobacter spp. , Klebsiella spp. , and Raoultella spp . Conclusions: Individuals with CRC in these cohorts harbored a higher relative abundance of sulfur-metabolizing enzymes, supporting the concept that microbial metabolism of dietary sulfur to hydrogen sulfide may contribute CRC carcinogenesis. Although specific bacterial species have been linked to CRC, sulfur-metabolizing genes are distributed across many taxa, suggesting that microbial function rather than composition may better explain disease risk. The consistency of these associations across ages suggests that early or prolonged exposure to sulfur-rich dietary patterns may promote a gut microbial environment capable of generating carcinogenic metabolites and support further mechanistic studies examining how diet and microbial function interact to influence CRC development.