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ABSTRACT Background A novel individualized antitachycardia pacing (IATP) algorithm using the post‐pacing interval for real‐time control has been introduced. Performance information is limited to a small safety and feasibility study with additional single‐center and case studies. A larger‐scale analysis is needed to better understand algorithm performance. Methods Deidentified remote monitoring transmissions from devices with the IATP therapy applied were randomly selected. Rhythms were classified and effects of the novel algorithm were assessed. For monomorphic ventricular tachycardias (MVTs) proportions of successful therapy, shock‐free episodes, and acceleration were calculated using generalized estimating equations to correct for multiple episodes and compute statistics of the algorithm's performance. Results There were 2259 MVT episodes in 336 patients. IATP succeeded in 87.1% of MVT episodes with 89.9% of MVT episodes ultimately free of shock therapy. Based on multivariate analysis, significant factors in therapy success were programming of at least the recommended number of sequences (90% at least recommended vs 73%, p = 0.00088) and female sex (95% for females vs 86%, p = 0.002). A trend to higher success was found for MVT with a cycle length of 320 ms or greater (90% vs. 83%, p = 0.10). The IATP accelerated 3.6% of MVT episodes. None of the available factors was significantly associated with acceleration in the multivariate analysis. Conclusions The IATP algorithm succeeded in a large proportion of MVT episodes and with low acceleration in patients randomly selected from remote monitoring transmissions. Using at least the recommended number of sequences had the strongest association with successful therapy.

Objective: To assess the efficacy of trichloroacetic acid (TCA) as treatment for high-grade cervical intraepithelial neoplasia (CIN 2 or 3). Methods: Retrospective study of patients with CIN 2 or greater treated with TCA from 2016 to 2022. Patients who desired future childbearing had a satisfactory colposcopy and had not received prior treatment for CIN. Patients were offered excision as initial treatment and for lesions that did not regress. TCA was discussed as an alternative, off-label treatment. Under colposcopic guidance, 85% TCA was applied to the transformation zone and distal endocervix. Patients were followed with colposcopy and cytology every 3–6 months and subsequently underwent excision or reapplication of TCA. Primary outcomes were regression and remission after a minimum of 6 months of treatment with TCA. Results: A total of 43 patients elected treatment with TCA. The mean age was 28.6 years with a median follow-up time of 12 months. The majority of patients were nonsmokers (95.3%) and White (73.9%). Pretreatment diagnosis was CIN3 and CIN2 in 32.6% and 67.4% of cases, respectively. After a median of three TCA treatments, 23.3% regression and 55.8% remission were noted for an overall cytological response rate of 79.1%. 16.3% required excision within 1 year. There were no cervical cancer diagnoses. The median time to regression and remission was 9 months and 6 months, respectively. Conclusion: In patients with high-grade CIN, treatment with TCA may have favorable short-term outcomes. TCA may represent an alternative to excision in reproductive-aged patients, though additional studies are needed with a larger cohort in a prospective manner.

Background: Addressing social determinants of health in patient care helps hospitals better understand the non-medical factors influencing patients’ health outcomes. Objectives: The objective of this study was to evaluate the correlation between hospital characteristics, county determinants, and the systematic recording of health-related social needs among general and surgical acute care hospitals in the United States. It focused on the hospital’s routine collection of data on patients’ health-related social needs, such as transportation, housing, and food insecurity. Design: A cross-sectional retrospective study design was utilized. Methods: All hospitals that completed the American Hospital Association Annual survey (n = 2254) were included in the study. A series of multinomial logistic analyses were conducted. Results: The relative risk of hospitals routinely collecting health-related social needs data is 67% lower in for-profit hospitals and 90% higher in not-for-profit hospitals compared to government hospitals. Hospitals that are part of a system are 1.5 times more likely to routinely collect data on social needs. In addition, counties with higher household income have a statistically significant higher relative risk of hospitals collecting data on social needs, though the magnitude of the difference is small. The relative risk of hospitals collecting social needs data, but not routinely, is 2 times higher in teaching hospitals and 3 times higher among system hospitals. Conclusion: Our research strongly indicates that understanding and addressing these inherent hospital-related factors are essential for effectively integrating social determinants of health into routine healthcare data collection practices. Establishing more robust guidelines and standardization in these practices may enhance hospitals’ ability to document and utilize health-related social needs information, ultimately driving improved patient outcomes and supporting more equitable care.

604 Background: The addition of OFS to standard endocrine therapy (ET) improves iDFS for preM women with early-stage hormone receptor positive (HR+) breast cancer (BC). Incomplete OFS occurs in a subset of women, the long-term clinical significance of which is unclear. This study evaluates local sE2 levels in preM women receiving OFS with an oral SERD in the neoadjuvant (NA) setting. Methods: The EOP is a I-SPY2 sub-study investigating NA endocrine-based strategies in pts with HR+ HER2- Stage 2/3 BC predicted to have lower benefit from chemotherapy. Pts were randomized to oral amcenestrant 200 mg/d, alone or in combination with either letrozole 2.5 mg/d or abemaciclib 150 mg bid. Additional pts were randomized to a standard of care (SOC) arm consisting of an aromatase inhibitor. All PreM pts received OFS with monthly GnRHa up to 2 wks prior to C1D1 of study therapy. Pts were treated for 6 months prior to surgery. sE2 levels were collected locally prior to each GnRHa injection. Tumor Ki67 was assessed at 3 weeks and surgery, and associated with sE2 level. Statistical significance was determined using a two-sided Student’s t-test and a significance level 0.05. Results: Between 5/2021-8/2022, 74 pts were enrolled to an amcenestrant containing arm, 40 of whom were preM. 38/40 pts had at least one local sE2 level measured in follow up. Of these 38 pts (median age 45 years), 37 suppressed sE2 into the postmenopausal (postM) range at one or more follow-up timepoints. Of the 37 pts that completely suppressed into the postM range, 6 pts had sE2 levels rebound into the preM range (mean 319 pg/mL, range 20-848 pg/mL) with peak sE2 levels occurring at a median of 12 weeks from C1D1. One pt never suppressed to the postM range (peak sE2 1227 pg/mL) and was found to have an ovarian cyst after 3 months on amcenestrant, requiring surgery. One additional pt had multiple ovarian cysts (sE2 84 pg/mL). Median age of the 7 pts who had sE2 rebound was 43 years. There was no significant difference in Ki67 at 3 weeks and surgery between pts whose sE2 levels remained suppressed (median Ki67 2.0%) compared to those whose estradiol rebounded into the preM range or never suppressed (median Ki67 1.5%). In the 5 pts whose sE2 rebounded to > 200 pg/mL, all pts had tumor Ki67 < 10% at 3 weeks and surgery. Between 12/2022 and 8/2023, 20 pts were enrolled to AI +/- OFS and 11 pts were preM. Of the 11 preM pts, all pts suppressed sE2 to the postM range. No SOC patients had sE2 levels rebound into the preM range. Conclusions: In this study of neoadjuvant oral SERD with monthly OFS, 7/38 (18.4%) preM pts had sE2 levels remain or rebound into the preM range. sE2 levels did not appear to impact Ki67 suppression on NA ET. Work up for ovarian cysts should be considered in pts with symptoms, or significantly elevated or persistent sE2 levels. Clinical trial information: NCT01042379 .

612 Background: EOP, an I-SPY2 sub-study, evaluates the tolerability and activity of novel endocrine strategies in stage 2/3 breast cancer (BC) patients (pts) predicted to have lower chemotherapy benefit. Laso, a selective estrogen receptor modulator (SERM), has shown favorable toxicity profile and activity in HR+/HER2- endocrine-resistant metastatic BC. Methods: Pts with Stage 2/3 HR+/HER2-, MammaPrint (MP) low risk BC were enrolled. Pts with MP High1 BC were included if clinically node-negative. Pts received oral laso 5 mg daily for six 28-day cycles. Laso was continued until the day prior to surgery. Premenopausal pts received ovarian function suppression (OFS) starting C2D1. The primary endpoint was feasibility (>75% of patients completing >75% study therapy). Baseline (T0), 3-wk (T1) biopsies, and the surgical specimen (T3) was assessed centrally for Ki-67. Breast MRI functional tumor volume (FTV) was performed at T0, T1, 12 weeks (T2), and pre-operatively (T3). Blood was collected for tumor informed ctDNA at T0, T1, T2, T3. Advance event (AE) was assessed using CTCAE V5. Results: From 3/2023 to 5/2024, 20 pts were enrolled. Median age 50.5 years, 50% premenopausal, and 1 male pt. 60% cN0, 80% MP low-risk signature. 18 (90%) pts completed >75% study therapy. Two pts discontinued treatment due to pt preference. Median Ki67 at T0 was 14.7%. At T1, 87.5% of pts remained or suppressed Ki67 to <10% and 37.5% suppressed to <2.7%. Ki67 at T1 was similar between pre-and postmenopausal pts despite OFS (Table). The median MRI FTV was 8.4 cc at T0, and 3.4 cc at T3. Median % FTV reduction from T0 to T3 was -47.5%. 2/20 pts (10%) achieved a modified PEPI score of 0. No patients achieved completed pathological response. Of the 16 pts with RCB results, 2 (12.5%) RCB-1, 6 (37.5%) RCB-2, 8 (50%) RCB-3 disease. 14 pts had ctDNA available at T0. 4/14 were ctDNA+ at T0, 2 of whom became ctDNA negative, and 2 remained ctDNA+. 10/14 pts were ctDNA negative at T0, 8 of whom remained negative, 2 became positive at T1 then cleared. All AEs were grade(G) 1 except 1 pt with G2 hot flashes. Most common AEs include hot flashes (85%), constipation (50%), fatigue (50%), and nausea (35%). One pt had G3 hypersensitivity and hypertension, both unrelated to therapy. Conclusions: Neoadjuvant laso demonstrates a favorable AE profile and promising anti-tumor activity in suppressing 3-wk Ki67 and MRI FTV change in pts with HR+ HER2-negative early BC. Ki67 suppression in premenopausal pts was seen in the absence of OFS. Clinical trial information: NCT01042379 . Ki67 expression at pre-treatment, and 3-wk time point. All Patients(n=20) Premenopausal (n=10) Postmenopausal (n=9) Median Ki67 expression Baseline 10.0% 12.5% 10.0% 3-wk 5.1% 3.0% 6.0% Number of pts with Ki67 expression <10% at 3-wk 87.5% 1 87.5% 85.7% Number of pts with Ki67 expression <2.7% at 3-wk 37.5% 50% 28.6% 1 Include the one male pt.

e15045 Background: Increased cancer cell mitosis in tumor tissue is widely regarded as an indicator of aggressive disease, a predictor of shorter survival, and an indicator of response to specific anthracycline based chemotherapies. Circulating tumor cells (CTCs) are cancer cells that detach from primary tumors, enter the bloodstream, and seed metastatic sites, which in patients (pts) with metastatic breast cancer (mBC) are also predictors of poor prognosis and reduced therapy response. Furthermore, small preliminary studies have identified a specific subtype of mitotic CTCs that appears to correlate with poor survival rates compared to CTC detection alone. However, larger studies have yet to be conducted to validate the clinical utility of mitotic CTCs. In this large multi-institutional prospective study, we isolated CTCs from the blood of n = 155 mBC pts to subtype mitotic CTCs to assess progression-free survival (PFS) and overall survival (OS) over 2 years. Methods: Peripheral blood samples (7.5ml) were prospectively collected from n = 155 mBC pts progressing on systemic therapies and prior to new systemic therapy induction (i.e., chemotherapy n = 90, hormone therapy n = 13, immunotherapy n = 51, targeted therapy n = 62). Samples were processed using CellSieve microfilters to isolate CTCs via size exclusion and fluorescently stained for CD45, Cytokeratin, and DAPI. CTCs were imaged, enumerated, and subtyped based on the presence of ≥1 mitotic event, using established visual indicators. PFS and OS were assessed over 2 years by censored univariate and multivariate analyses. Results: CTCs were detected in ~45% (n = 70/155) of pts, while mitotic CTCs were identified in a subset of this group, ~23% (n = 35/155). The presence of any CTC was associated with poor outcomes (PFS HR = 2.16, 95%CI = 1.4-3.2, p = 0.0002 and OS: HR = 2.51, 95%CI = 1.5-4.0, p = 0.0002). The presence of mitotic CTCs correlated with significantly poorer outcomes (PFS: HR = 5.6, 95%CI = 3.1-10.2, p < 0.0001 and OS: HR = 7.3, 95%CI = 3.7-14.5, p < 0.0001). Overall, pts with no CTCs had a median PFS (mPFS) of 7 months and median OS (mOS) of 24 months, pts with non-mitotic CTCs had a mPFS of 6 months and mOS of 15 months; pts with both CTCs and mitotic CTCs had a mPFS of 3 months and mOS of 5 months. Notably, 97% of pts with a mitotic CTC progressed within 6 months, regardless of systemic therapy type. Interestingly at 2 years, a sole non-progressive pt with a mitotic CTC was receiving alpelisib (a specialized PI3KCA inhibitor). Conclusions: Overall, the detection of CTCs indicated poor outcomes in pts, with mitotic CTCs correlating with significantly more aggressive disease and further reduced survival rates regardless of systemic therapy type. This study highlights the need for larger, more comprehensive studies to expand upon and validate these findings.

3008 Background: Numerous studies have demonstrated the prognostic value of ctDNA analysis after neoadjuvant chemotherapy for early-stage high-risk breast cancer. Few studies have characterized ctDNA in pts receiving NET for early-stage hormone receptor positive (HR+)/HER2- BC that is predicted to benefit less from chemotherapy. Methods: Cell-free DNA (cfDNA) was isolated from 432 plasma samples from 108 pts enrolled in the I-SPY2 EOP trial. Pts had Stage 2/3 HR+/HER2-, MammaPrint low or high risk 1 BC. Pts were randomized to one of 7 neoadjuvant-based treatment arms including arms containing AI, Z-endoxifen, Lasofoxifene, vepdegestrant (ARV-471), and Abemaciclib. Pts were treated for 6 months prior to surgery. Blood was collected at baseline (T0), 3 weeks (T1), 12 weeks (T2), and 6 months (T3). A personalized ctDNA test (Signatera) was designed to detect up to 16 patient-specific mutations (from whole-exome sequencing of pretreatment tumor) in cfDNA by ultra-deep sequencing. The chi-square test was used to assess associations between categorical variables, and the Wilcoxon rank-sum test was used to evaluate differences in medians. Results: ctDNA information was available for 101 patients at baseline (T0) (Table 1). At T0, 36 (35.6%) patients were ctDNA-positive. 23/36 (63.9%) became ctDNA-negative and 13/36 (36.1%) remained ctDNA-positive. At T0, 65/101 patients (64.4%) were ctDNA-negative. Of these, 57 (87.7%) remained negative, while 8 (12.3%) became ctDNA-positive at T1 before reverting to ctDNA-negative. A higher percentage of ctDNA-positive patients at T0 were cN+ compared to ctDNA-negative pts (p = 0.036, 64% vs. 40%). Additionally, ctDNA-positivity at T0 was strongly associated with higher Ki67 (p = 0.03) and larger functional tumor volume by MRI at baseline (p = 0.03). T3/T4 and high-grade tumors at baseline were also associated with having ctDNA positivity at baseline, though this was not statistically significant (p = 0.34 and 0.058, respectively). Conclusions: In this study of pts with Stage 2/3 HR+ HER2- BC with largely MammaPrint low risk signatures, over one-third of pts had detectable ctDNA at baseline. Detectable ctDNA at baseline was associated with cN+ disease, larger FTV, and high baseline Ki67. The majority of pts with positive ctDNA at baseline cleared the ctDNA on NET. Clinical trial information: NCT01042379 . Clinicopathologic characteristics of EOP patients. All Patients(N=101) Age at screening 55 (27-80) years* Clinical N Stage Node+ (cN+) 49 (48.5%) Node- (cN-) 52 (51.5%) SET status High 84 (83.2%) Low 14 (13.9%) Missing 3 (2.97%) MammaPrint (MP) risk** High risk 1 (H1) 15 (14.9%) Low risk 86 (85.1%) *Mean(min-max). **H1: MP score between 0 and -0.57; low: MP score between 0 and 0.355.

12011 Background: Patients (pts) with high HCT-Comorbidity Index scores (HCT-CI of ≥3), older age (≥65 years), and/or who are frail per gait speed (<0.8 meters/second) have increased morbidity and mortality after allo-HCT compared to younger and healthier counterparts. We report the phase II analysis (PIIA) and interim phase III primary outcome analysis (PIIIA) of a seamless phase II/III prospective, randomized clinical trial conducted at 11 transplant centers to test new approaches to improve quality of life (QOL) in this population. Methods: Phase II compared specialist-administered supportive and palliative care (SPC), patient-administered management of comorbidities (MC, e.g. physical exercise, stress reduction, etc), both (SPC+MC), and usual care (UC) for change in Functional Assessment of Cancer Therapy – Bone Marrow Transplantation (FACT-BMT) QOL scores from baseline to day 90 (D90). Pts deceased prior to D90 were assigned FACT-BMT score=0. The winning phase II arm moved forward versus UC in phase III. Results: PIIA was done after enrolling 35 pts to each of the 4 study arms. Calculating the difference between FACT-BMT scores on D90 minus baseline, excluding missing data, indicated that only SPC resulted in a small improvement in QOL compared to either MC or SPC+MC (Table); hence SPC was the winning phase II arm. The PIIIA was conducted after enrolling 158 SPC pts and 153 UC pts. The SPC and UC arms were well balanced with median age (both 68 years), HCT-CI ≥3 (49% vs 55%), frailty per gait speed (13% vs 12%), female sex (41% vs 34%), non-white race (9.5% vs 11.5%), and Hispanic or unreported ethnicity (7.7% vs 5.7%), respectively. After median follow-up of 362 days, 45 pts had died in each arm. The mean QOL difference between D90 and baseline was 2.83 for SPC and 4.27 for UC (difference of differences, -1.44, 95% CI of difference, -5.03 to 2.14, p=0.43). Fitting a generalized linear model that included baseline, D30, and D90 values and testing the null hypothesis that the slope of scores differs between SPC and UC resulted in p=0.85. Using the Kaplan Meier method, no difference in survival was observed across arms (HR 1.13 [0.75-1.73]). Conclusions: Specialist-administered palliative care showed no meaningful improvement in QOL, nor a survival advantage, compared to usual care in frail, older and comorbid allo-HCT recipients, resulting in the cessation of this Phase II/III trial. Analysis of the whole patient population for primary and secondary outcomes is in progress. Clinical trial information: NCT03870750 . Change in FACT-BMT (D90 value minus baseline value) comparing the 4 arms of phase II. Group Mean difference (sd) Median difference (range) SPC (n=28) -2.93 (28.52) 0.25 (-102 to 38.22) CM (n=18) -18.37 (33.80) -9.50 (-98.33 to 11) SPC+CM (n=27) -15.76 (32.69) -7.67 (-90 to 32)

7014 Background: Mosun is a CD20xCD3 bispecific antibody that can be administered in the outpatient setting for a fixed duration. Intravenous Mosun is approved for the treatment of relapsed/refractory FL after ≥2 prior lines of therapy. Mosun SC achieved high response rates with manageable safety in patients with 3L+ FL in a pivotal Phase II study (Bartlett et al. ASH 2024). We report the efficacy and safety of Mosun SC in patients with previously untreated high-tumor burden FL in the Phase II MorningSun study (NCT05207670). Methods: Patients with previously untreated high-tumor burden FL, per GELF criteria, were enrolled into this cohort. Mosun SC was administered with step-up dosing in Cycle (C)1 (Day [D]1, 5mg; D8, 45mg; D15, 45mg) then 45mg on D1 for up to 17 cycles (1 year; 21-day cycles). Patients with a partial or complete metabolic response (CMR) after C17 could receive additional Mosun maintenance therapy (45mg every 8 weeks for up to 1 year). Corticosteroid prophylaxis to reduce the risk of cytokine release syndrome (CRS) was mandatory in C1–2 and optional thereafter. The primary endpoint was progression-free survival (PFS) rate at 24 months. Key secondary endpoints included objective response rate (ORR), time to response (TTR), and safety. Results: As of May 29, 2024, 102 patients were enrolled; 55 patients had completed initial treatment (17 cycles), 31 had discontinued (most commonly due to progressive disease [n=19] and adverse events [AEs; n=4]), and 16 were ongoing initial treatment. Forty-two patients received maintenance treatment, and this was ongoing in 38 patients. Median age was 65 years (range: 24–86); 52.0% of patients were female. Most patients had Ann Arbor stage III/IV (91.2%) and a FLIPI score ≥2 (78.4%). Median duration of follow-up was 13.9 months. The 12-month PFS rate was 82.8% (95% confidence interval [CI]: 73.0–89.3). ORR was 87.3%; 60.8% of patients had a CMR. Among the 89 patients with a response, the median TTR was 2.7 months (range: 1.2–5.8). The most common AEs (≥30%) were injection-site reaction (57.8%), fatigue (42.2%), CRS (34.3%), headache (31.4%), and nausea (30.4%). Grade ≥3 AEs and serious AEs (SAEs) were reported in 44.1% and 29.4% of patients, respectively. CRS events were all Grade 1/2 and SAE of CRS occurred in 10.8% of patients (Table); all events resolved. Conclusions: Mosun SC demonstrated promising efficacy in patients with previously untreated high-tumor burden FL. The manageable safety profile, including rate of CRS, supports the administration of fixed duration Mosun SC in an outpatient setting. Additional data, including cytokine profiling and T/B/NK dynamics, will be presented. Clinical trial information: NCT05207670 . CRS events, n (%) PatientsN=102 Any grade 35 (34.3) Grade12 30 (29.4)5 (4.9) SAE 11 (10.8) ManagementSteroidsTocilizumabSteroids + tocilizumabFluidsICU admission 8 (7.8)6 (5.9)3 (2.9)3 (2.9)2 (2.0)