Citations

7067 Background: High intensity induction with regimens such asDA-EPOCH-R, CODOX-M/IVAC-R and HyperCVAD are often used for young patients with DHL/THL despite no overall survival (OS) benefit compared to R-CHOP. Reports on the application of CODOX-M/IVAC-R are subject to selection bias as only young fit patients can tolerate it. We aimed to investigate outcomes difference between CODOX-M/IVAC-R and DA-EPOCH-R in patients ≤ 60 years with DHL/THL diagnosed via FISH. Methods: Retrospective review of DHL/THL patients from the Mayo Clinic diagnosed between July15th 2010-October19th 2023 treated with CODOX-M/IVAC-R or DA-EPOCH-R at age of up to 60 years. Event free survival (EFS) was defined as time from diagnosis to progression, relapse, next line of treatment or death from any cause. Results: 113 patients were included; CODOX-M/IVAC-R (N=49) and DA-EPOCH-R (N=64). Patient and disease characteristics are in table. 80% (N=39) achieved CR on end of treatment (EOT) PET CT with CODOX-M/IVAC-R compared to only 58% (N=37) with DA-EPOCH-R. CODOX-M/IVAC-R was associated with superior EFS on univariate (HR=0.54, 95%CI=0.31-0.97) and multivariable analysis adjusted for age, BCL2 vs BCL6 translocation and receipt of consolidation ASCT (aHR=0.53, 95%CI=0.29-0.95), however, there was no significant influence on OS (aHR=0.97, 95%CI=0.50-1.91). At a median follow-up of 5.3 years and 3.3 years for the CODOX-M-IVAC and DA-R-EPOCH group respectively; EFS was superior in the CODOX-M/IVAC-R group having 1, 2 and 5 years EFS of 68.3%, 64.1 and 61.5% respectively compared to 52.4%, 48.9% and 39.5% respectively in the DA-EPOCH-R group (p=0.035). 33%(16/49) of the CODOX-M/IVAC-R patients had R/R disease (No CR on EOT PET CT or relapsed) with a median OS of 10.3 months compared to 33.7 months in the R/R DA EPOCH-R group (54%, 35/64). Number of patients who were able to receive salvage ASCT, CAR T and Allo-SCT were 5, 17 and 4 respectively in the DA EPOCH-R group compared to 1, 6 and 3 patients respectively in the CODOX-M/IVAC-R group. None died of regimen toxicity in both groups. 19% underwent ASCT consolidation after CR with initial induction (11 patients in each group); no OS was noticed however consolidation with ASCT was associated with increased EFS regardless of the induction regimen with best outcomes being in the CODOX-M/IVAC-R group (P=0.0072). Conclusions: Our study showed that young patients with DHL/THL who received CODOX-M/IVAC-R had superior EFS compared to DA-EPOCH-R with no OS benefit. CODOX-M/IVAC-R can spare patients receiving more subsequent therapies. Patients who have R/R disease following CODOX-M/IVAC-R have poor outcomes. [Table: see text]

5589 Background: Imlunestrant is a next-generation oral SERD designed to deliver continuous estrogen receptor (ER) target inhibition aimed to improve outcomes for patients (pts) with ER+ cancers. In the first-in-human Phase 1a/1b EMBER trial (NCT04188548), imlunestrant showed favorable safety, pharmacokinetics, and clinical benefit in pre-treated pts with ER+ advanced breast cancer or EEC. Here, we report updated imlunestrant monotherapy data and the first clinical data of imlunestrant + abemaciclib in ER+ EEC pts from EMBER. Methods: Eligible pts had ER+ EEC previously treated with (or deemed inappropriate for) platinum-containing chemotherapy. Prior fulvestrant or aromatase inhibitor therapy was not allowed. In Phase 1a, pts received imlunestrant alone, and in Phase 1b, pts were randomized (1:1) to imlunestrant alone or with abemaciclib. Plasma samples were collected at baseline (all pts) and at cycle 2 (monotherapy pts) for ctDNA analysis (Guardant 360 assay) to correlate with clinical benefit. Primary endpoints were RP2D of imlunestrant monotherapy and in combination. Secondary endpoints included safety, tolerability, and overall response rate (ORR), clinical benefit rate (CBR: complete or partial response, or stable disease ≥24 weeks), and progression-free survival (PFS) using RECIST v1.1. Results: Overall, 72 pts were treated; 39 pts received monotherapy (33 at 400mg [RP2D] and 6 at 800mg po daily) and 33 pts received imlunestrant (29 at 400mg and 4 at 800mg po daily) + abemaciclib (150mg po twice daily). Baseline characteristics, safety, and preliminary efficacy are presented (Table). For monotherapy, the most common TEAEs (all grade/grade 3) were nausea (36%/3%), diarrhea (26%/0), urinary tract infection (26%/3%), and abdominal pain (21%/8%). For imlunestrant + abemaciclib, the most common TEAEs (all grade/grade 3) were diarrhea (88%/3%), nausea (67%/0), fatigue (49%/9%) and anemia (46%/12%). In the monotherapy arm, pts with deeper (≥ 50%) declines in ctDNA variant allele frequency had a higher CBR (4/7 vs 4/17). Conclusions: Imlunestrant, as monotherapy or with abemaciclib, appears safe and tolerable with preliminary evidence of efficacy in pts with metastatic ER+ EEC. Clinical trial information: NCT04188548 . [Table: see text]

TPS1127 Background: Patients with estrogen receptor-positive (ER+) metastatic breast cancer (mBC) may develop resistance to endocrine therapy (ET), particularly following treatment with a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i), potentially driven by a mutation in the ERa-coding gene, ESR1. Lasofoxifene (LAS), an oral, next-generation ET and ER breast antagonist, was evaluated in two phase 2 studies of women with ER+/HER2- mBC and an ESR1 mutation who had disease progression on previous ET and CDK4/6i. The ELAINE 1 trial showed numerically greater progression-free survival (PFS, median ~6 vs 4 mos; P=0.138), objective response rate (ORR, 13% vs 3%; P=0.124), and clinical benefit rate (CBR, 37% vs 22%; P=0.117) with LAS monotherapy versus the ER degrader fulvestrant (fulv), with a favorable safety profile (1). The single-arm, ELAINE 2 trial demonstrated that LAS plus abemaciclib (Abema) was well tolerated with a median PFS of ~13 mos, ORR of 56%, and CBR of 66% (2). Based on these data, the phase 3, registrational, ELAINE 3 trial was initiated. Methods: ELAINE 3 (NCT05696626) is an open-label, phase 3, multicenter study evaluating the efficacy, safety, and tolerability of LAS plus Abema versus fulv plus Abema. Key inclusion criteria are pre- and postmenopausal women and men aged ≥18 yrs; ER+/HER2-, locally advanced and/or mBC (measurable and/or non-measurable disease); ≥1 acquired ESR1 mutation; progression on an aromatase inhibitor plus palbociclib or ribociclib as their first hormonal treatment for advanced/mBC; and ≤1 line of chemotherapy in the advanced/metastatic setting. Patients will be randomized 1:1 to receive LAS 5 mg/day plus Abema 150 mg BID, or fulv 500 mg IM on days 1, 15, and 29, then once monthly plus Abema 150 mg BID. Treatment will continue until progression, death, unacceptable toxicity, or withdrawal from the study. The primary endpoint is PFS; key secondary endpoints are ORR, overall survival, CBR, duration of response, and time to response. Time to cytotoxic chemotherapy, quality of life, and safety will also be evaluated. Blood samples for circulating tumor DNA (ctDNA) will be collected for genomic analyses at screening, at weeks 4 and 8 and every 8 weeks thereafter, and at the final visit. Outcomes with LAS/Abema and fulv/Abema will be compared using a stratified Cox proportional hazards model and stratified logrank test. Expected PFS is ≥10.3 mos for LAS/Abema and 7 mos for fulv/Abema (PFS hazard ratio of 0.68 at final analysis). The target sample size is 400, to achieve 90% power with a one-sided type I error rate of 0.025 after 285 PFS events. Full recruitment is expected to occur over 18 mos at approximately 125 global sites. 1. Goetz MP, et al. Ann Oncol. 2023;34:1141-1151. 2. Damodaran S, et al. Ann Oncol. 2023;34:1131-1140. Clinical trial information: NCT05696626 .

AbstractINTRODUCTIONWhile Latin America (LatAm) is facing an increasing burden of dementia due to the rapid aging of the population, it remains underrepresented in dementia research, diagnostics, and care.METHODSIn 2023, the Alzheimer's Association hosted its eighth satellite symposium in Mexico, highlighting emerging dementia research, priorities, and challenges within LatAm.RESULTSSignificant initiatives in the region, including intracountry support, showcased their efforts in fostering national and international collaborations; genetic studies unveiled the unique genetic admixture in LatAm; researchers conducting emerging clinical trials discussed ongoing culturally specific interventions; and the urgent need to harmonize practices and studies, improve diagnosis and care, and use affordable biomarkers in the region was highlighted.DISCUSSIONThe myriad of topics discussed at the 2023 AAIC satellite symposium highlighted the growing research efforts in LatAm, providing valuable insights into dementia biology, genetics, epidemiology, treatment, and care.

Introduction Empowering people living with multimorbidity (multiple chronic conditions) to gain greater confidence in managing their health can enhance their quality of life. Education focused on self-management is a key tool for fostering patient empowerment and is mostly provided on an individual basis. Virtual communities of practice (VCoP) present a unique opportunity for online education in chronic condition self-management within a social context. This research aims to evaluate the effectiveness/cost-effectiveness of individualised, online self-management education compared with VCoP among middle-aged individuals living with multiple chronic conditions. Methods and analysis People aged 30–60, living with ≥2 chronic conditions and receiving care in primary care (PC) centres and outpatient hospital-based clinics in Madrid and Canary Islands will enrol in an 18-month parallel-design, blinded (intervention assessment and data analysts), pragmatic (adhering to the intention-to-treat principle), individually randomised trial. The trial will compare two 12-month web-based educational offers of identical content; one delivered individually (control) and the other with online social interaction (VCoP, intervention). Using repeated measures mixed linear models, with the patient as random effect and allocation groups and time per group as fixed effects, we will estimate between-arm differences in the change in Patient Activation Measure from baseline to 12 months (primary endpoint), including measurements at 6-month and 18-month follow-up. Other outcomes will include measures of depression and anxiety, treatment burden, quality of life. In addition to a process evaluation of the VCoP, we will conduct an economic evaluation estimating the relative cost-effectiveness of the VCoP from the perspectives of both the National Health System and the Community. Ethics and dissemination The trial was approved by Clinical Research Ethics Committees of Gregorio Marañón University Hospital in Madrid/Nuestra Señora Candelaria University Hospital in Santa Cruz de Tenerife. The results will be disseminated through workshops, policy briefs, peer-reviewed publications and local/international conferences. Trial registration number NCT06046326 .

Background: Peripheral Artery Disease (PAD) ranks as the 10th primary cause of mortality and the 11th for disability among all cardiovascular diseases in the U.S. Method: We employed the Global Burden of Disease 2019 framework. PAD non-fatal health outcomes were analyzed using the DisMod MR 2.1 (Bayesian meta-regression tool) and determined fatal health outcome with the cause of death ensemble model (CODEm), segmented by age, gender, year, and location from 1990-2019 across the U.S. Results: The annual percentage change (APC) revealed a 26% (9.9-12.4 million) increase in overall prevalence and incidence, a significant 152% (5,757-14,527) rise in deaths, and a 98% (119,253-236,031) uptick in DALYs during 1990-2019. Notably, while the age-standardized incidence rate dipped by 28% (267-193), death and DALY rates climbed by 33% (1.7-2.27) and 11% (36-39) respectively. Delaware witnessed the highest APC in deaths 118% (2.33-5.08) per 100,000, trailed by Colorado with a 58% (35-55) rise in DALYs. Individuals under 70 experienced a 118% (1052-2294) surge in APC for deaths and a 28% (458,357-588,135) increase in incidence. In absolute numbers, males bore a heavier PAD burden, yet females exhibited elevated age-standardized rates from 1990-2019. Conclusion: The study underscores a concerning rise in PAD in the U.S. from 1990-2019, accounted for 1.52% deaths of all cardiovascular related casualties in 2019. Delaware and Colorado have notably high increases in PAD-related outcomes. From both a clinical and public health perspective, addressing high fasting plasma glucose and sodium-rich diets is crucial, as they stand as leading risk factors in PAD's burgeoning prevalence.