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MM-259: Impact of the International Myeloma Working Group (IMWG) SLiM Criteria on Multiple Myeloma Management: A Tertiary Care Center Experience
No full textMultiple myeloma (MM) is a hematologic malignancy characterized by the proliferation of plasma cells. IMWG\u27s introduction of the SLiM criteria in 2014 expanded the diagnosis of MM. Our retrospective study evaluated the adoption and impact of these criteria at Henry Ford Cancer Institute (HFCI), focusing on patient demographics and outcomes of those diagnosed exclusively using the SLiM criteria. Methods: Electronic medical records at HFCI (January 2015–December 2023) were reviewed to identify MM patients meeting at least one SLiM criterion (≥60% plasma cells, free light chain (FLC) ratio \u3e100, or MRI lesion), excluding those with CRAB features. Data on demographics, staging, treatment, and outcomes (through December 2024) were analyzed. Results: Between 2015 and 2023, 495MMpatients were diagnosed; 190 met at least one SLiM criterion. After excluding 177 with CRAB features, 13 patients remained who were diagnosed solely by SLiM criteria. Of these, 6 had plasma cells \u3e60%, 11 had FLC ratio \u3e100, and 3 met MRI criteria. The mean age was 63.6 years; 53.8% were female, 53.8% African American, and 38.4% Caucasian. High-risk cytogenetics were present in 53.8% patients. By Revised International Staging System (R-ISS) staging, 61.5% of patients had stage 1, 30.7% had stage 2, and 7.6% had stage 3 disease. Twelve patients received treatment with induction regimen, which included bortezomib, lenalidomide, dexamethasone (VRd) (n = 9), daratumumab-VRd (n = 1), carfilzomib, lenalidomide, dexamethasone (KRd) (n = 1), or bortezomib, dexamethasone (Vd) (n = 1), all starting treatment at diagnosis. Among them, there was one death (hospice, age/comorbidities), two relapses (both in remission after second-line therapy), and nine remained in remission. One patient, diagnosed in 2017, has not required treatment to date. Conclusion: Our study highlights real-world data on the impact of the IMWG SLiM criteria for MM diagnosis. Patients diagnosed solely based on SLiM criteria, who would previously have been classified as having smoldering myeloma, were treated at diagnosis, reflecting real-time adoption of the updated guidelines. This underscores the positive impact and practical applicability of the revised criteria. Interestingly, one untreated patient has not progressed, suggesting the need for appropriately powered randomized studies to better understand outcomes in this specific subset of patients
In silico evaluation of the interaction of P-gp and 3A4 substrates with the WEE1 inhibitor Debio 0123 and clinical application in the Debio 0123-104 combination trial with carboplatin and etoposide
No full textBackground: Debio 0123 is an oral, brain-penetrant, highly selective WEE1 kinase inhibitor currently being investigated in several clinical trials in patients with advanced solid tumors both as monotherapy and in combination. In vitro, Debio 0123 can inhibit and induce cytochrome P450 (CYP) 3A4 and inhibit P-gp. Methods: A physiologically-based pharmacokinetic (PBPK) model using Simcyp Population Based Simulator was developed for Debio 0123 to evaluate its perpetrator effect on sensitive substrates of CYP3A4 and P-gp. A second model was developed for etoposide as victim drug. Both were combined to assess the risk of clinical drugdrug interaction (DDI) between Debio 0123 and etoposide. Plasma etoposide concentrations were simulated following single and three daily doses of etoposide 100 mg/m2 IV administered concomitantly with, or without, 520 mg oral (PO) Debio 0123. The Debio 0123 model was developed using in vitro and clinical data from previous Debio 0123 clinical trials. Results: No clinically significant DDIs were predicted between Debio 0123 given for 3 consecutive days and the CYP3A4 probe substrate, midazolam. When PO or IV administration of midazolam was simulated, the 90%CI of the geometric mean ratio (GMR) for AUCinf and Cmax, alone versus in combination with Debio 0123, entirely fell within 0.9 and 1.3. A weak DDI was predicted towards the P-gp probe substrate dabigatran etexilate. When given orally, AUCinf and Cmax GMR of dabigatran with, or without, Debio 0123 were 1.87 and 1.93, respectively. Administration, for 3 consecutive days, of Debio 0123 combined with IV etoposide was predicted to have no effect on etoposide exposure (90%CI of GMR for both AUC and Cmax within 0.80-1.25). Accordingly, the design of Debio 0123-SCLC-104 trial with Debio 0123 administered in combination with carboplatin and etoposide (NCT05815160 - ASCO 2025 # 495064) was developed with standard doses of IV etoposide. To confirm the absence of DDI, PK samples were collected in the trial. No major changes were noted in the observed etoposide exposure across Debio 0123 dose levels (200 to 400 mg) after one or three days of co-administration in adult SCLC participants that recurred or progressed after previous platinum treatment. Etoposide PK observed in the study was also in line with literature data (US label Etopophos 2011). Debio 0123 PK was consistent with data previously reported for monotherapy (Abstract #3120 ASCO 2024). Conclusions: Overall, these results indicate that there is no relevant PK interaction between Debio 0123 and IV etoposide. For concomitant medications that are P-gp substrates, only a weak DDI is expected with Debio 0123. Furthermore, the absence of significant DDIs predicted with CYP3A4 substrates suggests that Debio 0123 can be combined with a wide range of therapies
Individual participant data meta-analysis comparing neoadjuvant to perioperative chemoimmunotherapy in early-stage non-small cell lung cancer according to PD-L1 status
No full textBackground: Neoadjuvant and perioperative chemo-immunotherapy are two standard-of-care treatment options for patients with early-stage Non-Small Cell Lung Cancer, both of which improve event-free-survival (EFS). A recent reconstructed individual patient data (IPD) meta-analysis found no difference in EFS between these approaches. However, another patient-level analysis of CheckMate trails 816 and 77T reported that perioperative nivolumab significantly improves EFS, particularly in the PD-L1 negative subgroup. Our study aims to compare neoadjuvant and peri-operative chemo-immunotherapy based on PD-L1 status using reconstructed IPD. Methods: Data were collected from Kaplan-Meier curves of eight randomized trials, including five perioperative and three neoadjuvant trials. Only trials with Kaplan-Meier curves stratified by PD-L1 levels were included. Data extraction, IPD reconstruction, and survival analyses were conducted using the IPDfromKM tool. Patients were stratified according to their PD-L1 tumor proportion score (TPS) as negative (#1%), positive (1-49%) and high (50%). No significant differences in EFS were observed between perioperative and neoadjuvant approaches among patients with any PD-L1 TPS (P=0.634) or within any PD-L1 subgroup (negative: P=0.449; positive: P=0.311; high: P=0.334). Conclusions: This reconstructed IPD meta-analysis found no significant difference in EFS between perioperative and neoadjuvant chemo-immunotherapy in ES-NSCLC, regardless of PD-L1 status. Treatment decisions should consider other patient-specific factors beyond PD-L1 status. Larger randomized trials are needed to further identify patients who may benefit from additional immunotherapy after surgery
Vascular heterogeneity influences treatment response in pancreatic cancer
No full textPancreatic ductal adenocarcinoma (PDAC) remains a highly lethal malignancy, in part due to its heterogeneous tumor microenvironment. Most PDAC tumors are poorly vascularized and embedded within densely fibrotic stroma; however, in prior computational analyses, we identified a subset of PDAC tumors with hyper-vascular features. In this study, we sought to determine the extent of vascular heterogeneity in PDAC and its functional consequences. Analysis of human tumor specimens revealed that approximately 10-20% of human tumors display features of hyper-vascularity. Using a panel of clonal murine cell lines that recapitulate this heterogeneity, we demonstrate that VEGFA-mediated angiogenesis does not account for the increased vessel density. Functionally, we further show that hyper-vascular tumors display enhanced sensitivity to both chemotherapy and anti-angiogenic therapy. These findings help explain the limited efficacy of VEGFA-targeted therapies in unselected PDAC cohorts and highlight vessel density as a potential biomarker for patient stratification
Feasibility Project To Assess the Use Of An AI-supported Phase 3 Cardiac Rehabilitation Program
No full textIntroduction: Phase 3 cardiac rehabilitation (CR) programs are typically utilized as a strategy to help patients maintain the health gains achieved during phase 2 CR. However, due to many barriers for both patients and CR facilities, only a small percentage of individuals participate in these hospital-based programs. Home-based CR offers a promising convenient alternative, that can eliminate many common barriers to patients (e.g. transportation, limited class times) as well as facilities (limited space and staff). Purpose: To evaluate the feasibility of a home-based, virtual CR digital platform (KENTO Health, INC) following participation in CR. Primary outcomes were weekly engagement in the platform and synchronized coach visits. Secondary outcomes assessed the program\u27s impact on QoL, depressive symptoms, and physical activity at 60 days. Design: Single-center, open-label, non-randomized, prospective pilot study. Methods: Eligible patients who had completed or were unable to continue their Phase 2 CR were consented and enrolled into the pilot study where they were given a tablet preloaded with the Kento Health application (KHapp) and an activity tracker (Garmin). The intervention consisted of a 12-week hybrid Phase 3 CR program featuring synchronous coaching, continuous physiologic monitoring (i.e. heart rate and steps), and AI-personalized educational content. Patients completed questionnaires online at the beginning of the study and at 60-days. The questionnaires given were the Patient Health Questionnaire-9 (PHQ-9), Dartmouth COOP, Godin Leisure-Time Exercise Questionnaire, and Net Promoter Score (NPS). A paired samples test was used to compare changes over time with an alpha level set at \u3c 0.05 (SPSS 22.0 IBM). Results: 20 out of 24 patients who were enrolled and consented completed the initial and 60-day questionnaires. Average age was 69 + 12, with 45% female and 71% Black. The percentage of subjects that attended weekly coach visits was 79%. Satisfaction of the program at 60-days, as measured by the NPS, was 96%. Patient reported quality of life (QOL), as measured by the Dartmouth COOP total score was maintained [21 + 5 to 19 + 5 (p = 0.135)] 60 days after completion of CR. The Dartmouth COOP subscale score regarding \u27how would you rate your health compared to 4 weeks ago\u27 was improved (p = 0.025). Physical activity levels and self-reported depression were also maintained based on the Godin (p = 0.973) and PHQ (p = 0.283) scores, respectively. Conclusions: This pilot study supports the feasibility of a home-based virtual Phase 3 CR program delivered synchronously with weekly coach visits and AI driven education. Improvement in patient reported health at 60 days was observed. Further research is warranted to explore home-based, virtual programs as a strategy to improve outcomes in patients who participate in CR.
TCT-688 Utility of Intravascular Ultrasound in Optimizing Outcomes Following Coronary Covered Stent Deployment
No full textBackground: Intravascular ultrasound (IVUS) has been shown to enhance outcomes in percutaneous coronary interventions (PCI), particularly through improved stent sizing and expansion. In this study, we investigated the role of IVUS in patients who required covered stents for the treatment of coronary artery perforation (CAP). Methods: We conducted a retrospective analysis of 131 patients treated with either Papyrus or GraftMaster covered stents for CAP between December 2014 and January 2024. Patients were divided into two cohorts: those who received IVUS-guided PCI and those who did not. The primary outcomes assessed included procedural success, stent thrombosis, in-stent restenosis, and the requirement for additional covered stents. Statistical comparisons were performed using chi-square tests, with significance defined as p \u3c 0.05. Results: Of the 131 patients, 34 (26.0%) underwent IVUS-guided stent implantation. Procedural success was significantly higher with IVUS (88.2% vs. 65.8%, p = 0.000047), and stent thrombosis was lower (0.0% vs. 7.9%, p = 0.0079). In-stent restenosis rates were similar (12.9% vs. 16.1%, p = 1.00). The need for a second covered stent was markedly reduced with IVUS (5.9% vs. 34.2%, p = 0.000008). [Formula presented] Conclusion: Use of IVUS in the management of CAP requiring covered stents was associated with improved procedural success and lower rates of both stent thrombosis and need for additional stents. These findings suggest that IVUS may play an important role in optimizing outcomes when deploying covered stents in emergent PCI settings. Categories: IMAGING AND PHYSIOLOGY: Imaging: Intracoronar
TCT-981 Cardiogenic Shock Following Transcatheter Tricuspid Valve Replacement: A Single Center Experience
No full textBackground: The potential for acute-on-chronic RV failure remains unclear following valve implantation. In this study, we describe the incidence of cardiogenic shock after TTVR. Methods: This is a retrospective analysis of 122 patients who underwent TTVR for severe TR at Henry Ford Hospital between March 2024 and April 2025. Clinical courses were reviewed to identify cases of hemodynamic compromise meeting SCAI Stage C shock criteria within 24 hours post-procedure. RV dysfunction was assessed by visual estimation and graded on a four-point scale: none, mild, moderate, and severe. Results: Of the 122 patients, 3 (2.45%) developed SCAI Stage C cardiogenic shock within 24 hours of the procedure. At baseline, 28 patients (22.9%) had ≥moderate RV dysfunction. The incidence of post-procedural shock was numerically higher among patients with ≥moderate RV dysfunction (7.14%) compared to those ≤mild RV dysfunction (1.06%), although this difference did not reach statistical significance (RR 6.71; 95% CI: 0.64–70.5; p=0.150). All three patients demonstrated rapid clinical improvement following volume optimization and achieved hemodynamic stability within 12-hours. Notably, none progressed to SCAI Stage D shock and all patients avoided in-patient and 3-month mortality. [Formula presented] Conclusion: The incidence of cardiogenic shock following TTVR is low, even among patients with advanced RV dysfunction. In cases of acute heart failure, rapid clinical improvement with volume optimization was observed. These findings support thoughtful cardiac prehabilitation and support the overall safety of TTVR in patients with advanced RV dysfunction. Categories: STRUCTURAL: Valvular Disease and Intervention: Tricuspi
TCT-1100 Transcatheter Versus Surgical Aortic Valve Replacement in Patients Aged 50 to 65 Years: A Propensity Score-Matched Retrospective Study
No full textBackground: Transcatheter aortic valve replacement (TAVR) is increasingly considered for younger patients, yet data comparing outcomes versus surgical AVR (SAVR) in those aged 50–65 years remain limited. Methods: We conducted a retrospective study of patients aged 50–65 years undergoing TAVR or SAVR using the TriNetX database. Propensity score matching (1:1) minimized the effects of baseline differences. Outcomes included a composite of all-cause mortality and stroke, permanent pacemaker implantation (PPM), acute kidney injury (AKI), major bleeding, and myocardial infarction at 30 days. Additional one- and five-year outcomes included all-cause hospitalization, valve degeneration and thrombosis, and redo AVR. Hazard ratios (HRs) with 95% confidence intervals (CIs) were used to estimate the overall effect size. Results: A total of 1698 matched pairs were analyzed. At 30 days, TAVR was associated with a lower risk of the mortality/stroke (HR 0.63; 95%CI 0.46–0.86), major bleeding (HR 0.16; 95%CI 0.13–0.19), and AKI (HR 0.50; 95%CI 0.38–0.65). At 1 year, TAVR had a higher risk of individual all-cause mortality (HR 1.46; 95%CI 1.09–1.94) with no difference in the composite outcome. At 5 years, TAVR showed a higher risk of mortality/stroke (HR 1.50; 95%CI 1.27–1.78; Figure) and valve degeneration (HR 1.81; 95%CI 1.43–2.28), with no difference in hospitalization or redo AVR. [Formula presented] Conclusion: In patients aged 50–65 years, TAVR was associated with fewer short-term complications. However, at 1 year, mortality was higher with TAVR, and by 5 years, the risks of mortality/stroke and valve degeneration increased in comparison to SAVR. Categories: STRUCTURAL: Valvular Disease and Intervention: Aorti
TCT-274 pLVAD-Supported Cardiogenic Shock in STEMI vs. NSTEMI: Does Myocardial Infarction Type Matter? Insights from RECOVER III and NCSI
No full textBackground: Use of Impella improves survival in patients with STEMI and cardiogenic shock (CS), however there is limited data on NSTEMI-CS. Methods: Patients with AMI-CS who underwent revascularized with Impella were included from the NCSI (NCT03677180) and RECOVER III (NCT04136392), both multi-center, single arm studies. Patients were stratified by MI type. Clinical characteristics, hemodynamics and outcomes were compared. Subgroup analyses by shock stage at time of index procedure was performed. Mortality was evaluated at discharge, 30 days and 1 year. Multivariable logistic regression adjusted for demographics, comorbidities, SCAI stage, and coronary anatomy was also performed. Results: Among 775 AMICS patients (79% STEMI, 20.3% NSTEMI]), patients with NSTEMI had more comorbidities, extensive coronary disease, and higher pre-Impella IABP use (12.7% vs. 7.3%, p=0.03). STEMI patients more often had out-of-hospital-cardiac arrest (34.8 vs. 15.5%, p\u3c0.0001) and higher baseline lactate levels (6.3 ± 4.7 vs. 5.2 ± 4.3, p=0.06). Pre-Impella hemodynamics and use of vasoactive agents were similar between groups. Unadjusted mortality was comparable at discharge, 30 days and 1 year (p=0.71, 0.85, and 0.85, respectively), with similar outcomes across shock stages (Figure). MI type was not independently associated with survival, though STEMI trended toward higher 1-year survival (OR 0.80, 95% CI: [0.63,1.01] p=0.06). [Formula presented] Conclusion: NSTEMI patients had similar outcomes to STEMI patients, despite higher risk features when treated with Impella. Categories: CORONARY: Hemodynamic Support, Cardiogenic Shock and Cardiac Arres
TCT-1082 Impact of Weekend Admission on Outcomes in STEMI Patients Undergoing Early Percutaneous Coronary Intervention: A National Retrospective Cohort Study
No full textBackground: ST-elevation myocardial infarction (STEMI) is a time-sensitive emergency requiring rapid reperfusion, usually via percutaneous coronary intervention (PCI). Despite improvements in door-to-balloon times, concerns remain about the “weekend effect,” where patients admitted on weekends may experience delays and worse outcomes. Limited data exist on whether this effect persists among STEMI patients undergoing PCI within 24 hours. This study evaluated whether weekend admission independently impacts in-hospital outcomes in this population. Methods: We used the 2017–2022 National Inpatient Sample (NIS) to identify adults with a primary diagnosis of STEMI who underwent PCI within 24 hours. The exposure was weekend admission (AWEEKEND). The primary outcome was in-hospital mortality. Secondary outcomes included cardiogenic shock, acute kidney injury (AKI), vasopressor use, sepsis, CVA, ICU admission, arrest, CABG, IABP, Impella, and ECMO. Of 117,462 patients, 28,632 (24.4%) were weekend admissions. We used survey-weighted logistic regression to adjust for patient, clinical, and hospital factors. Results: Weekend admission was associated with higher mortality (aOR 1.204; CI 1.124–1.29; p \u3c 0.001), cardiogenic shock (aOR 1.189), AKI (aOR 1.163), vasopressor use (aOR 1.138), sepsis (aOR 1.136), CVA (aOR 1.302), ICU admission (aOR 1.17), and cardiac arrest (aOR 1.215). No differences were found for transfusion, GI bleeding, CABG, Impella, or ECMO. [Formula presented] Conclusion: Weekend admission was independently associated with worse outcomes despite early PCI, suggesting persistent disparities in STEMI care. Categories: CORONARY: Acute Coronary Syndrome