Citations

Abstract Background Teclistamab (Tec) and Talquetamab (Tal) are the two first FDA approved bispecific antibodies (BsAb) for the treatment of patients (pts) with relapsed/refractory multiple myeloma (RRMM). Both Tec and Tal should be initiated with step-up dosing (SUD) in an inpatient (IP) setting to mitigate the risk of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), per US label. However, standard of care practice continues to evolve and more pts receive SUD as an outpatient (OP) to reduce healthcare resource utilization and improve pt convenience. While most real-world evidence has focused on clinical and safety outcomes of pts treated with Tec and Tal, pt experience associated with these novel BsAb therapies is relatively unexplored. Methods HealthTree Foundation, a multiple myeloma pt advocacy group which provides enrolled pts with information on treatments, community groups, and research participation, surveyed RRMM patients who have received Tec or Tal. Eligible pts who completed the treatment experience survey had at least 4 months of follow-up after starting BsAb. The survey was fielded from May 2024 through June 2025. Data collection followed IRB-exempt protocols with informed consent. Results A total of 32 patients (24 Tec, 8 Tal) completed the survey. The median age was 70 years, 50% were male, and 84% were white. Most pts (n=24; 75%) received SUD at their primary oncology clinic (n=19, 59% at an academic center; n=5, 16% at local community center), and 8 (25%) at an academic center which was not their primary oncology clinic. All pts who received SUD at an academic center that was not their primary oncology clinic later transitioned to their local community clinic post-SUD and reported being satisfied or very satisfied with their transition of care experience. Overall, most pts (n= 21; 66%) received their entire step-up dosing during a single hospitalization, while some (n=6; 19%) received all doses of the SUD during separate hospitalizations for each dose. About 13% (n=4) received all SUD in an OP setting, and 3% (n=1) received SUD in a hybrid setting (mix of IP and OP). Although 85% (n=27) of the pts received IP SUD, 66% (n=21) would have preferred IP SUD in one hospitalization, while the remaining 34% (n=11) would have preferred OP or hybrid SUD. Among pts who received IP SUD (n=27), almost a quarter reported a preference for either OP (n=4; 15%) or hybrid SUD (n=2; 7%) and 78% (n=21) preferred one IP hospitalization for SUD. The factors influencing their preference for the setting of SUD in this IP sub-group were feeling more secure with IP monitoring (78%), convenience (26%), less worry about staying near healthcare centers (15%), being able to stay with their local physician (11%), staying closer to home (7%), and lower costs to the pt (4%). Among pts receiving OP SUD (n=4), 75% (n=3) preferred fully OP SUD and 25% (n=1) preferred hybrid SUD because of convenience (n=2; 50%), lower cost to pt (n=1; 25%), flexible dosing schedule (n=1; 25%), and feeling of security with IP monitoring (n=1; 25%). All the pts receiving hybrid SUD (n=1) preferred fully OP SUD due to convenience. Although Tec and Tal are subcutaneous (SC) injections, when patients were asked to compare the options of BsAbs with comparable efficacy and safety profile, they favored SC injection (n= 22; 69%) over intravenous infusion (n = 3; 9%), while 22% (n=7) had no preference for mode of drug administration. The challenges that impacted pt experience with Tec or Tal were treatment side effects (Tal pts: n=6, 75%; Tec pts: n=9, 38%) and distance or travel time to the treatment facility (Tal pts: n=2, 25%; Tec pts: n=4; 17%). Other reasons included caring for others, continuing to work, cost and insurance, lack of caregiver/care partner, being away from home, unavailability of the therapy in community setting near home, and eligibility criteria. Conclusions Most pts in this study received SUD at their primary oncology clinic. While most pts received IP SUD and preferred a single planned IP visit, one third preferred OP or hybrid SUD due to convenience. As the field moves toward OP-only SUD, this study underscores the need to consider pt preferences. There is an unmet need for community clinics providing SUD options closer to pt homes.

Abstract Background: Social determinants of health (SDOH) are critical drivers of cancer care access and outcomes. In multiple myeloma (MM), access to cellular therapies including autologous stem cell transplantation and CAR-T therapy often depends on formal or informal caregiver support. Traditional SDOH measures (e.g., race, income, or education) are often used as proxies for access to care; however, these measures may overlook individual realities pertaining to cellular therapies where a caregiver is generally required. In response to feedback from a HealthTree Patient Advisory Board questioning the practice of inferring caregiver support, this study evaluated a simple survey question by a large cross-sectional survey. Methods: After development of a dedicated single-question (“What best describes your current caregiving support?”) through iterative feedback from the Patient Advisory Board and MM experts, four key answers were settled on: (1) cohabitation with dedicated caregiver(s) to support care (“family support”); (2) presence of non-cohabiting caregiver(s) to provide dedicated support (“external support”); (3) lack of dedicated caregiver, hence support is arranged when needed (“arrangeable support ”); or (4) lack of dedicated caregiver, hence finding any support is a struggle (“inadequate support”). We deployed this new demographic question from February through July 2025 through HealthTree. Responses were analyzed across SDOH variables using Fisher exact or chi square tests, and random forest classifiers were employed for predictive modeling. Results: Of 1231 respondents, 71% had dedicated caregivers (68%, n=839, with family support, and 3%, n=41, with external support). In contrast, 23% (n=287) of patients routinely arranged support while 5% (n=64) had inadequate support (struggle to find support). The inadequate-support group had significant demographic differences from the sample as a whole: a higher proportion were women (78% vs 56%, p = 0.04), Black (9% vs 4%, p < 0.01), lived >50 miles from their treatment center (17% vs 6%, p < 0.01), and had an annual income <$50,000 (17% vs 6%, p = 0.02). This group had a numerically higher proportion of patients whose employment status was disabled (12% vs 5%, p=0.08) as well. No proportion difference in age (67 ± 9 yr), military status, or severity of diagnosis - precursor disease (17%) v. multiple myeloma (81%). Rates of inadequate support were overall low in patients who lived with only their spouse (1%) or lived with their spouse & children (3%). In contrast, rates of inadequate support were higher (than 5%) in patients who lived alone (21%), divorced (20%), lived with adult children (14%), lived with friends (13%), separated (11%), or widowed (9%) (p < 0.001). However, the arrangeable-support group comprised 12% of patients who lived only with their spouse, 19% of patients who lived with their spouse and children, and 61% of patients who lived with their adult children (p < 0.001). Finally, a random forest classifier failed to identify any individual in the inadequate-support category, suggesting that unmeasured or more complex patterns may underlie this classification. Conclusions: To our knowledge, this is the largest analysis of caregiver support and its relationship with other SDOH in patients with MM to date. Despite the importance of caregiving to transplantation and CAR-T therapy, we found that 5% of patients with MM struggle to find caregiver support; this figure likely underestimates the true prevalence, given potential selection bias among patients who are digitally engaged through the HealthTree platform. Even among patients who lived with their spouses, an additional 10-20% of patients routinely had to arrange caregiving support on a visit-by-visit basis; for patients who lived with their adult children, this proportion was over 60%. The requirement to arrange caregiving support can create time toxicity and financial toxicity for patients, although these factors were not directly queried in our study. Finally, caregiver availability cannot be routinely inferred from traditional SDOH variables. Our data highlight the importance of including caregiver status as a standard demographic question in clinical and research settings. Further interventions are needed to improve caregiver support for vulnerable patients with MM as well as to reduce the duration of caregiver requirements for procedures such as CAR-T therapy.

Abstract Background Accurate reconstruction of electronic health record (EHR) treatment sequences is essential for leveraging real-world data (RWD) in clinical research and trial-eligibility platforms in multiple myeloma (MM). However, inconsistencies in RWD treatment documentation and the complexity of line-of-treatment (LOT) assignments in MM hinder reproducibility and limit comparisons against published trials. To address these limitations, we developed HEAL-MM, an automated rule-based algorithm that systematically parses structured medication data to calculate LOTs and segment treatment into standardized, clinically meaningful phases. The algorithm is designed to be interpretable, adaptable to evolving therapeutic frameworks, and compatible with widely adopted EHR data standards. Here, we report its real-world validation against expert-adjudicated treatment sequences to assess concordance, identify edge-case failure points, and support RWD integration. Methods A stratified cohort of 100 MM patients (9,136 structured treatment events) was curated from 114 unique healthcare systems compiled from the multi-institutional HealthTree Foundation harmonized registry. Cohort selection was randomized to ensure coverage across diagnostic eras (pre-2010, 2015–2020, 2022–2025) and treatment exposures, including CAR T-cell therapies, bispecific antibodies, and anti-CD38-based regimens. HEAL-MM sequenced MM regimens chronologically and applied predefined logic rules to identify LOT transitions, the initiation of a new therapeutic course based on drug changes, treatment gaps, and procedural anchors such as stem cell transplant or CAR T. Within each LOT, the algorithm segments and labels therapy into phases, clinically distinct intervals (e.g., induction and maintenance) using rule-based clinical logic. Outputs were benchmarked against expert-labeled adjudications. Concordance was evaluated using concordance index (C-index), stratified by patient, LOT depth and diagnostic era. Results: HEAL-MM demonstrated high concordance with expert-labeled treatment sequences: 0.94 for LOT identification, 0.98 for treatment phase segmentation, and 0.96 for phase label assignment. Achieving complete agreement with all expert annotations in 90% of patients for LOT assignment, 94% for the number of treatment phases identified, 77% for the specific labels applied to each phase, and 75% across all three dimensions simultaneously. Among discordant patients, the absolute difference in final LOT count was 0.5 ± 0.9. Performance was highest in early lines (LOTs 1–3; C-index: 0.97), with seven patients showing discrepancies at this stage. Concordance declined in later lines (LOT ≥4; C-index: 0.87), where 50% of the discordant cases (n=4) were attributable to misclassifications in earlier LOTs, such as medication restarts following >3-month gaps, demonstrating the compounding effect of early errors on longitudinal accuracy. Temporal stratification revealed improved accuracy in post-2020 cases (C-index: 0.94) compared to 2015–2020 cohorts (0.91), reflecting the increasing adoption of structured treatment standards and EHR data quality improvements. To assess HEAL-MM performance at clinically significant junctures, we analyzed treatment transitions that initiated a new LOT or marked a change in phase, achieving C-indices of 0.97 for LOT transitions, 0.97 for treatment phase shifts, and 0.94 for phase label assignment. Conclusions: HEAL-MM provides a validated, scalable solution for standardizing MM treatment structures in RWD environments, as it accurately detects the exact treatment entry of a new LOT 97% of the time. This rule-based framework enables reproducible LOT and phase assignment across heterogeneous EHR systems, supporting real-time cohort identification across institutions and EHR platforms. The algorithm's modular design allows for continuous integration of novel therapeutic categories and evolving treatment logic. While the algorithm maintained high fidelity overall, early-stage misclassifications consistent with increased heterogeneity and documentation ambiguity occasionally propagated downstream, underscoring the compounding effect of upstream errors in longitudinal reconstruction. With its generalizable structure and compatibility with industry-standard data models, HEAL-MM lays the foundation for structured treatment reconstruction in MM across RWD infrastructure and serves as a transferable blueprint for other hematologic malignancies.

Abstract Description Generation of T cells requires dynamic epigenetic alteration of histones to control gene expression at each developmental stage. The Class I deacetylases HDAC1, HDAC2, and HDAC3 have been shown to have 3 functions: adaptor, decrotonylase, and deacetylase activity. The relative importance of each function in T cells is not known. CD2icre HDAC3 cKO mice develop severe colitis and demonstrate that HDAC3 is required during thymocyte development for positive selection, DP survival, and CD4 lineage commitment. Recently, a mutation was identified in HDAC3 that eradicated deacetylase activity (“VRPP”). We generated a novel mouse model with Cre-mediated deletion of endogenous HDAC3 and linked re-expression of HDAC3 VRPP, which maintained adaptor function but lacks both deacetylase and decrotonylase enzymatic activity. Similar to CD2icre HDAC3 cKO mice, HDAC3 VRPP mice have a block in positive selection due to failure to down regulate RORγt and decreased DP cell survival due to increased expression of P2RX7, demonstrating that HDAC3 enzymatic activity is required for these functions. However, when the positive selection defect is bypassed in HDAC3 VRPP mice, CD4+ lineage commitment is restored. Strikingly, this mouse does not develop spontaneous colitis even up to one year of age, although T cell development is still impaired. Thus, there are different roles for HDAC3 enzymatic vs. adaptor function during T cell development which are made evident in HDAC3 VRPP mice. Funding Sources NIAID RO1 AI150100; T32 AI170478; Mayo Clinic Graduate School of Biomedical Sciences Topic Categories Lymphocyte Differentiation and Peripheral Maintenance (LYM)

Abstract Description Inflammatory bowel disease (IBD) affects between 1-3 million people in the United States, and patients present with symptoms including diarrhea, rectal bleeding, and fatigue. ST8Sia6 is a sialic acid transferase that adds terminal a2,8 disialic acids to O-linked glycoproteins, and a SNP in ST8Sia6 is associated with Crohn’s Disease. We have found that ST8Sia6 knockout (KO) and heterozygous (het) mice exhibit a 30-fold increase in small bowel immune infiltrate, along with an increased proportion of Th1 and pathogenic Th17 CD4 cells. These mice also exhibit activated gut epithelia, increased inflammatory cytokines, and increased innate cell activation, indicative of gut inflammation. Both ST8Sia6 KO and het mice exhibit increased weight loss and decreased survival when challenged with low dose dextran sodium sulfate-induced colitis. CellChat pathway analysis demonstrates enhanced TNF and IL-1 pathway activation in ST8Sia6 KO small bowel epithelium as compared to WT mice. In addition, ST8Sia6 KO small bowel epithelium produces significantly more CCL5, which may drive immune cell migration. These data demonstrate a role for ST8Sia6 in regulating gut immune homeostasis. As TNF blockade is a first line therapy for IBD patients, elucidating the role of ST8Sia6 in regulating this pathway is critical for a mechanistic understanding of IBD pathogenesis, and this may help to improve immunotherapy options for the disease. Funding Sources NIH R01CA243545 & NIH 5T32DK124190 Topic Categories Basic Autoimmunity (BA)

Abstract Introduction There are limited data on the impact of glucagon-like peptide-1 receptor agonist (GLP-1RA) on the risk of recurrent pouchitis after ileal pouch–anal anastomosis (IPAA) for ulcerative colitis (UC). Methods A retrospective cohort study was conducted in the TriNetX Research Network in adult patients with obesity and IPAA for UC with a history of pouchitis in whom a GLP-1RA was initiated compared to those patients in whom a GLP-1RA was not initiated. The primary outcome was the risk of recurrent pouchitis within 12 months. The secondary outcomes were mean number of antibiotic prescriptions, anti-diarrheal medication use, Crohns-like disease of pouch (CLDP), and pouch excision. One-to-one propensity score matching was performed. Results We identified 43 UC-IPAA patients with obesity and history of pouchitis (mean age 51.7 ± 14.7 years, mean body mass index [BMI] 34.4 ± 6 kg/m2, 60.4% female). After propensity score matching, the GLP-1RA cohort had a significantly decreased risk of recurrent pouchitis (26.3% vs 52.6%; adjusted odds ratio [aOR], 0.32; 95% CI, 0.12-0.84) compared to the control cohort. Mean antibiotic prescriptions were numerically lower in the GLP-1RA cohort (2 vs 4.4, P = .16). Anti-diarrheal medication use was lower in the GLP-1RA cohort (18.4% vs 47.3%; aOR, 0.23; 95% CI, 0.07-0.67). There was no difference in the risk of CLDP. Zero patients required pouch excision in both cohorts. Conclusion Our study in a small cohort of patients with UC-IPAA and obesity with a history of pouchitis showed that GLP-1RA use was associated with decreased risk of recurrent pouchitis and anti-diarrheal medication use.

The treatment landscape of invasive early-stage and metastatic breast cancer is evolving constantly. These NCCN Guidelines Insights focus on recent updates included in the most recent version (version 5.2025) of the NCCN Guidelines for Breast Cancer specific to workup, locoregional therapy, surveillance, and systemic neoadjuvant/adjuvant therapy recommendations for invasive, nonmetastatic breast cancer.

The NCCN Guidelines for Prostate Cancer provide a framework on which to base decisions for patients with prostate cancer across the disease spectrum. The Guidelines sections included in this article focus on metastatic castration-sensitive prostate cancer (mCSPC), nonmetastatic castration-resistant prostate cancer (CRPC), and metastatic CRPC (mCRPC). For patients with mCSPC, disease characteristics, such as whether metastases arose synchronously or metachronously and the degree of metastatic burden, impact therapy decisions, including how much treatment intensification is appropriate and when prostate-directed and/or metastasis-directed therapy should be considered. In the mCRPC setting, androgen deprivation therapy is continued with the sequential or concurrent addition of certain androgen receptor pathway inhibitors, chemotherapies, immunotherapies, radiopharmaceuticals, and/or targeted therapies. The NCCN Prostate Cancer Panel emphasizes a shared decision-making approach in all disease settings based on patient preferences, prior treatment exposures, biomarkers, the extent and location of metastases, symptoms, and potential side effects.

Objective: To evaluate whether effects of oral hormone therapy (HT) on risks of venous and arterial vascular events differ by baseline statin or aspirin use. Methods: We performed time-to-event analysis using data from the Women’s Health Initiative menopausal HT randomized trials to assess risk of thrombotic events. Women were randomized to oral conjugated equine estrogens (CEEs) alone or placebo among women with prior hysterectomy (n = 10,739), and CEE with medroxyprogesterone acetate (MPA) or placebo among women with an intact uterus (n = 16,608), stratified by baseline personal use of statins and aspirin. We evaluated risk of prespecified, adjudicated thrombotic events, including coronary heart disease, stroke, venous thromboembolism, and/or composite major adverse cardiovascular events, at 2 and 5 years. Results: Baseline statin use (n = 827 in CEE-alone trial; n = 1,115 in CEE+MPA trial) or aspirin use (n = 2,212; n = 3,431) was limited. At 5-year follow-up, coronary heart disease risk for CEE-alone versus placebo was hazard ratio (HR) = 0.81 (95% CI: 0.44-1.49) in statin users, similar to nonusers, HR = 1.07 (95% CI: 0.82-1.40). For CEE+MPA, there was also no difference by statin use, HR = 1.02 (95% CI: 0.55-1.89) and HR = 1.47 (95% CI: 1.13-1.90), respectively. Neither statin nor aspirin exposure significantly modified effects of HT on any arterial or venous thrombotic outcome at 2 or 5 years. Conclusions: In this secondary randomized clinical trial analysis, neither statins nor aspirin significantly modified effects of oral HT on key arterial or venous thrombotic outcomes at 2 or 5 years. Results, however, may be underpowered given low baseline exposure prevalence for both statins and aspirin.

Goals: This study aimed to assess perspectives and practices among expert gastroenterologists regarding the screening, diagnosis, and management of BE. Background: Significant variability in the management of Barrett’s esophagus (BE) persists among physicians despite the development and dissemination of several clinical practice guidelines. Study: An online survey was conducted with 38 expert gastroenterologists specializing in BE management. The 38-question survey evaluated demographics, medical management, and attitudes toward endoscopic treatment, with responses analyzed for trends and variations. Results: Of the 38 experts, 34 (89%) responded. Respondents were primarily male (85%), with 82% affiliated with academic hospitals and 53% clinically focused on BE. Half discussed BE risks during initial consultations for gastroesophageal reflux disease (GERD). Most (61.8%) agreed BE should be considered in women with chronic GERD, and 88.2% regularly used narrow-band imaging (NBI). However, 44% were neutral or disagreed with diagnosing BE based solely on community gastroenterologist biopsies, and acceptance of Wide-Area Transepithelial Sampling with 3D Analysis (WATS-3D) for Barrett’s esophagus diagnosis and surveillance was limited. Fifty-three percent recommended ablation for nondysplastic BE. Fifty-two percent recommended indefinite daily PPI therapy after complete eradication of intestinal metaplasia (CEIM), regardless of symptoms. When encountering cardia intestinal metaplasia after endoscopic eradication, 38% recommended ablation, while 47% continued surveillance. Conclusion: This study highlights substantial variations in the management of BE among expert gastroenterologists, despite the existence of updated guidelines. Identifying these discrepancies is crucial for optimizing care. Further efforts are needed to standardize practices and enhance the implementation of evidence-based guidelines in clinical settings.