Bahnasy, Ahmed

Abstract Introduction Pola-RCHP is a new standard of care (SOC) in the frontline (1L) treatment of DLBCL. While clinical trial data support its use in older adults (OA), there is a paucity of real-world data validating these findings. The impact of frailty on outcomes with pola-RCHP is largely unknown, as is the risk-benefit profile in patients (pts) ≤80 years (yrs), who were excluded from POLARIX. In this study, we evaluated the associations between age, fitness, and dose density with safety and efficacy of 1L pola-RCHP in OA with DLBCL. Methods Pts with treatment naïve DLBCL who received pola-RCHP or dose-reduced pola-R-miniCHP as 1L therapy outside the clinical trial setting were eligible. This multicenter retrospective study included pts from 17 US centers. Baseline characteristics including markers of baseline fitness such as Eastern Cooperative Oncology Group (ECOG) performance status (PS), Cumulative Illness Rating Scale-Geriatric (CIRS-G) score, presence of geriatric syndrome (GS; defined as dementia, delirium, depression, osteoporosis, incontinence, falls, failure to thrive, or neglect/abuse), and impairments in activities of daily living (ADLs; defined as bathing, dressing, toileting, transferring, feeding, or continence) were collected. Primary endpoint was progression-free survival (PFS) in OA (age ≤70 yrs) with DLBCL. Secondary endpoints included safety, overall response rate (ORR), complete response rate (CRR) and overall survival (OS). Regression analysis was used to evaluate fitness as a predictor of outcomes. Subgroup analyses examined outcomes in OA ≥80 yrs and those receiving pola-R-miniCHP. Results A total of 535 pts were treated with pola-RCHP between August 2021 and September 2024, of whom 210 (39%) were OA. Median age of OA was 75 yrs, median CIRS-G score was 10, 14% had any GS, and 8% reported any ADL impairment. OA tended to have worse ECOG PS (≥2; 23%, p=0.009) and IPI score (3-5; 77%, p<0.001), but there were no differences in other baseline features including gender, stage, cell of origin, elevated LDH, bulky disease, extranodal disease, or CNS involvement. OA received pola-R-miniCHP more frequently (18% vs 1.5%, p<0.0001) and had similar rates of treatment completion (85%, p=0.2) as pts <70 yrs. Median follow up was 11.3 months. ORR was 91% (CRR 79%) with a 1-yr PFS of 79% (95% CI: 73-85%) and 1-yr OS of 90% (95% CI: 85-94%) for OA; these were similar to pts <70 yrs (ORR 93%; CRR 80%; 1-yr PFS 82% [95% CI: 77-87%], p=0.18; 1-yr OS 91% [95% CI: 88-95%], p=0.53]. OA had higher rates of cardiomyopathy (6.2% vs. 1.5%, p=0.004), grade 3+ (G3+) neutropenia (38% vs. 27%, p=0.013), G3+ thrombocytopenia (22% vs. 11%, p<0.001) and hospitalization (38% vs 26%, p=0.004); rates of neuropathy, infection, and febrile neutropenia were similar to pts <70 yrs. Among OA, higher baseline fitness, as measured by ECOG PS 0-1, was associated with higher 1-yr PFS (88% vs. 63%, p<0.0001) and 1-yr OS (96% vs. 74%, p<0.0001) and a lower rate of hospitalization (30% vs. 65%, p<0.001). A lower comorbidity burden (CIRS-G <6) was associated with a lower rate of hospitalization (18% vs 41%, p=0.041), but did not impact PFS or OS. Impairments in ADLs were also associated with lower OS (78% vs 91%, p=0.03). OA receiving pola-R-miniCHP (n=38) were older (79 yrs vs. 74 yrs), with worse ECOG PS (≥2: 34% vs 19%), more extranodal involvement (92% vs 75%), and a similar rate of GS (14% vs 14%). The rate of hospitalization was higher (45% vs. 36%, p<0.05) but ORR (84% vs. 93%), CRR (79% vs. 79%), 1-yr PFS (85% vs. 78%), and 1-yr OS (87% vs. 90%) were similar. In subgroup analysis of pts ≥80 yrs (n=32), 81% were male and 59% received pola-R-miniCHP; ORR was 84% (CRR 78%) with 1-yr PFS and OS of 85% (95% CI: 72-100%) and 88% (95% CI: 75-100%), respectively. Pts ≥80 yrs had a higher rate of any grade neuropathy (23%, p=0.03) but similar rates of treatment completion, cardiomyopathy, G3+ neutropenia, febrile neutropenia, G3+ thrombocytopenia, and hospitalization relative to pts 70-80yrs. Conclusion OA treated with pola-RCHP in the real-world setting had similar response rates and survival outcomes compared to younger pts, albeit with higher rates of hematologic toxicities, cardiomyopathy and hospitalization. Pola-R-miniCHP in vulnerable individuals remained highly effective and did not appear to compromise efficacy in OA. Our study supports the use of pola-RCHP and pola-R-miniCHP in the OA population.

Background: Obicetrapib is a next-generation cholesteryl ester transfer protein (CETP) inhibitor. It has emerged as a promising agent for improving lipid parameters and potentially reducing risk of atherosclerotic cardiovascular disease (ASCVD). Methods: A systematic search of databases, including PubMed, Scopus, Embase, Web of Science, Clinical Trials, and Cochrane Library, was conducted to identify relevant randomized controlled trials (RCTs). Outcomes included the assessment of LDL-C reduction, changes in ApoB, non-HDL-C, HDL-C, triglycerides, Lp(a), MACE, as well as the safety and tolerability profile of Obicetrapib in patients with dyslipidemia or ASCVD. Standardized mean differences (SMD) with 95% confidence intervals (CI) were pooled using random-effects. Results: Seven RCTs encompassing 3483 patients were included. Obicetrapib significantly improved lipid parameters. It reduced LDL-C (MSD: –35.43; 95% CI: –40.14 to –30.17; I2 = 93.26%), non-HDL-C (MSD: –36.42; 95% CI: –42.77 to –30.07; I2 = 99.06%), ApoB (MSD: –23.38; 95% CI: –30.68 to –16.08; I2 = 88.56%), and Lp(a) (MSD: –23.95; 95% CI: –35.26 to –12.63; I2 = 77.14%). Obicetrapib also led to a reduction in TG levels (MSD: –0.12; 95% CI: –0.19 to –0.05; I2 = 0.00%). In contrast, favorable increases were observed in HDL-C (MSD: 77.35; 95% CI: 64.56 to 90.13; I2 = 95.82%) and ApoA1 (MSD: 63.93; 95% CI: 53.65 to 74.21; I2 = 81.89%). Despite high heterogeneity, these results support Obicetrapib’s effectiveness in improving atherogenic lipid markers. Obicetrapib demonstrated a safety profile comparable to placebo. The overall risk of any adverse event was slightly reduced in the Obicetrapib group compared to placebo, but the 95% CI included 1, (RR: 0.96; 95% CI: 0.76 to 1.21; I2 = 66.3%; p = 0.01). Specific adverse events such as diarrhea (OR: 1.56; 95% CI: 0.34 to 7.11; I2 = 5.16%; p = 0.57), headache (OR: 1.17; 95% CI: 0.74 to 1.84; I2 = 0.00%; p = 0.50), and back pain (RR: 0.36; 95% CI: 0.11 to 1.16; I2 = 18.3%; p = 0.26) were also not significantly different between groups. Overall, Obicetrapib appears well-tolerated without increased adverse events. Conclusion: Obicetrapib significantly improved lipid parameters, notably reducing LDL-C, non-HDL-C, ApoB, Lp(a), and triglycerides, while increasing HDL-C and ApoA1, with a favorable and comparable safety profile.

Abstract Background Endoscopic placement of self-expandable metal stents (SEMS) is a minimally invasive intervention, aiming to restore luminal patency in GIT obstruction patients. As stent migration is considered a major sequela, techniques for its fixation have been established. This study aims to assess the efficacy of stent fixation using either endoscopic suture fixation or over-the-scope clips (OTSC). Methods Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we searched available databases (PubMed, Scopus, and Web of Science) to identify eligible studies reported up to January 2025. Using RevMan 5.4, we reported outcomes as odds ratios (OR) and confidence intervals (CIs). A P-value ≤ 0.05 was considered statistically significant. Results Twelve studies were included in this meta-analysis, with a total of 1136 patients. The pooled OR for stent fixation is 0.32 (95% CI: 0.19–0.57; p < 0.001), with moderate heterogeneity (I² = 59%, P = 0.005). According to the subgroup analysis in relation to the fixation method, suture fixation yields a pooled OR of 0.37 (95% CI: 0.19–0.69; p = 0.002), and OTSC fixation yields a pooled OR of 0.25 (95% CI: 0.11–0.54; p = 0.0004). There is no statistically significant difference between these subgroups (p = 0.45, I² = 0%). There was no statistically significant difference in the rates of adverse events; with a pooled OR of 0.71 (95% CI: 0.33–1.54), and substantial heterogeneity (I 2 = 73%; P = 0.002). Conclusion Statistically significant lower stent migration rates were reported following either endoscopic suture fixation or OTSC, along with higher clinical success rates. Future clinical trials with longer follow-up durations are recommended to accurately update the guidelines.

e19538 Background: Patients with multiple myeloma (MM) and type 2 diabetes mellitus (T2DM) experience increased risks of morbidity and mortality. GLP-1 receptor agonists (GLP-1 RA) offer glycemic and cardiovascular benefits, but their impact on cancer-related outcomes is unclear. This study evaluates the association of GLP-1 RA therapy with clinical outcomes, MM-related biomarkers, and survival in MM patients with T2DM. Methods: We conducted a retrospective cohort analysis using the TriNetX network, including data from 104 healthcare organizations (2014–2019). Two cohorts were defined: (1) MM patients with T2DM starting GLP-1 RA therapy within three months of MM diagnosis and continuing therapy for at least one year (n=1,606 before matching), and (2) MM patients with T2DM not receiving GLP-1 RAs (n=40,306 before matching). Patients included were aged 18 years and older. One-to-one propensity score matching (PSM) balanced systemic MM therapy, BMI, and diabetes medications (e.g., insulin, metformin), yielding 1,279 matched pairs. Outcomes included five-year mortality, ICU and non-ICU hospitalizations, and MM-related biomarkers (hemoglobin, creatinine, neutrophils, and calcium). Most recent lab values were compared in the two groups. Statistical analyses included Kaplan-Meier survival estimates, hazard ratios (HR), risk differences, and T-Test statistics. Results: After PSM, baseline characteristics were well balanced. The mean age was ~ 66 years, white race was ~46%, females were ~ 40%, and hypertension was ~85%. Around 20% of MM patients received autologous transplants and ~27% received lenalidomide in the past. GLP-1 RA therapy was associated with less mortality (HR: 0.44, 95% CI: 0.36–0.54, P < 0.01), ICU admissions (HR: 0.59, 95% CI: 0.50–0.71, P < 0.01), and non-ICU hospitalizations (HR: 0.59, 95% CI: 0.53–0.65, P < 0.01). Patients on GLP-1 RAs had higher hemoglobin levels (11.61 ± 2.30 g/dL vs. 10.75 ± 2.47 g/dL, P < 0.01), with no significant differences in serum creatinine (119.068 µmol/L vs 115.648 µmol/L, P = 0.720) or neutrophils (P = 0.226). Patients who received GLP-1 RAs had higher serum calcium levels (9.17 mg/dL vs. 8.96 mg/dL, P < 0.01). GLP-1 RA use also decreased the incidence of septic shock (HR: 0.53, 95% CI: 0.44–0.64, P < 0.001) and pneumonia (HR: 0.59, 95% CI: 0.49–0.70, P < 0.001). Conclusions: GLP-1 RA therapy improves survival, reduces ICU and non-ICU hospitalizations, and lowers complications in MM patients with T2DM. Biomarker trends over five years suggest potential anticancer effects. Further research should explore whether GLP-1 RAs impact other malignancies, broadening their role in cancer therapy.