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Effectiveness and safety of apixaban vs. aspirin for primary prevention of stroke and bleeding risk among patients with atrial fibrillation: A Meta-analysis of randomized controlled trials including ARTESIA trial.
No full textBackground: Atrial fibrillation is a common arrhythmia that increases the risk of stroke. However, treatment of such patients with oral anticoagulants when compared with aspirin is not well established with uncertain benefits. Objective: We analyzed available study level data comparing Apixaban and Aspirin for efficacy and safety among atrial fibrillation patients. Methods: We performed a systematic literature search on PubMed, EMBASE, and ClinicalTrials.gov for relevant randomized controlled trials (RCTs) from inspection until August 10th, 2024, without any language restrictions. Odds ratios (OR) and 95% confidence intervals (CI) were pooled using a random-effect model, and a p-value of \u3c0.05 was considered statistically significant. Results: A total of 3 RCTs with 14,224 patients were included (7,129 in apixaban and 7095 in the aspirin group) in the analysis. The mean age of the patients in apixaban and the aspirin groups was 72.4 and 72.8 years, respectively. Pooled analysis of primary and secondary endpoints showed that apixaban significantly reduced the risk of stroke or systemic embolism by 47% (OR, 0.53(95%CI: 0.38-0.75), P\u3c0.001), stroke by 44% (OR, 0.56(95%CI: 0.44-0.70), P\u3c0.001), and ischemic stroke by 51% (OR, 0.49(95%CI: 0.29-0.81), P=0.01) when compared with aspirin. However, the risk of major bleeding (OR, 1.03(95%CI: 0.69-1.53), P=0.88), myocardialinfarction (OR, 0.97(95%CI: 0.76-1.23), P=0.78), and all-cause mortality (OR, 0.97(95%CI: 0.80-1.17), P=0.72) was comparable when compared with the aspirin group of patients. Conclusion: In this comprehensive analysis of randomized controlled trials data, the use of apixaban was associated with reduction in stroke or systemic embolism, and ischemic stroke, when compared with aspirin therapy. Major bleeding risk, and all cause mortality was comparable between both groups of patients
CT-1272: Bridging to Allogeneic Hematopoietic Cell Transplantation Following CD19-Directed CAR-T Therapy in Relapsed/Refractory Large B-Cell Lymphoma: A Systematic Review of Outcomes and Prognostic Indicators
No full textAnti-CD19 chimeric antigen receptor T-cell (CAR-T) therapies have reshaped the therapeutic paradigm for relapsed/refractory large B-cell lymphoma (R/R LBCL). Yet, real-world durability remains limited, with up to 60% of patients progressing within 1 year. Allogeneic hematopoietic cell transplantation (allo-HCT) is increasingly considered as consolidative or salvage therapy, though its role after CAR-T therapy remains ill-defined. Objective: To systematically evaluate published outcomes of allo-HCT following CAR-T therapy in R/R LBCL and identify clinical or biological predictors of benefit. Design: A systematic review was conducted according to PRISMA guidelines. PubMed, Embase, and ClinicalTrials.gov were searched for studies published from 2017 to 2025. Inclusion criteria encompassed prospective or retrospective series reporting outcomes of adult patients with R/R LBCL undergoing allo-HCT following CAR-T therapy. Data on overall survival (OS), progression-free survival (PFS), nonrelapse mortality (NRM), and graft-vs-host disease (GVHD) were extracted. Setting and Patients: Seven studies comprising 142 patients were included. Median age ranged from 48 to 61 years. Most received axicabtagene ciloleucel or tisagenlecleucel. The interval between CAR-T infusion and allo-HCT ranged from 50 to 120 days. Approximately 60% to 75% of patients underwent transplant in complete response (CR), while others proceeded with partial response or stable disease. Intervention: Allo-HCT following CAR-T, using reduced-intensity or myeloablative conditioning. Donor sources included matched unrelated (44%–58%), matched sibling (18%–33%), and haploidentical (up to 15%) donors. GVHD prophylaxis regimens varied, with the most common post-transplant regimens based on cyclophosphamide and tacrolimus. Main Outcome Measures: Across studies, 1-year OS ranged from 36% to 59%, with PFS ranging from 30% to 45%. NRM ranged from 17% to 22%. Acute GVHD grade ≥2 occurred in 28% to 36%, and chronic GVHD in up to 40%. Durable remissions were predominantly observed in patients bridged in CR with minimal disease burden and fewer than two intervening salvage lines after CAR-T therapy. Conclusions: Allo-HCT remains a feasible and potentially curative option in select patients following CD19-directed CAR-T therapy failure. Optimal candidates are those with early response and minimal disease pre-HCT. The heterogeneity of conditioning intensity, donor selection, and timing limits direct comparability. Prospective biomarker-guided trials are warranted to define transplant eligibility and improve sequencing after CAR-T therapy in R/R LBCL
NSCLC in the immunotherapy era: Trends in survival and disparities across demographic and socioeconomic groups
No full textBackground: Advanced non-small cell lung cancer (NSCLC) has historically been associated with poor survival outcomes. The introduction of immune checkpoint inhibitors in 2015 revolutionized treatment by improving survival, yet access to these therapies remains inequitable. This study examines survival trends in NSCLC before and after 2015, focusing on racial and socioeconomic disparities in the immunotherapy era. Methods: This population-based study utilized SEER registry 22 to evaluate survival disparities in NSCLC cases diagnosed between 2004 and 2020. Patients were stratified by stage (regional and distant), age, race, income, and sex. Survival outcomes, including median survival (MS) and five-year overall survival (5-Year OS), were compared using Kaplan-Meier analysis and log-rank tests to assess disparities across demographic and socioeconomic subgroups. Results: Among 591,525 NSCLC cases were included, with 355,283 diagnosed pre-2015 and 236,242 post-2015. MS improved from 11 months pre-2015 to 13 months post-2015 (p \u3c 0.001). Five-year overall survival increased from 16.8% pre-2015 to 19.6% post-2015, reflecting advancements in care over time. Racial disparities persisted across both periods. Non-Hispanic Black patients had the lowest survival rates, with five-year overall survival improving from 21.4% pre-2015 to 24.5% post-2015 in localized stages, compared to 25.7% and 29.2% for Non-Hispanic White patients. Among patients with distant-stage disease, survival improved marginally from 6.7% pre-2015 to 7.9% post-2015 for non-Hispanic Black patients, lagging behind non-Hispanic White patients, whose survival increased from 8.6% to 10.3%.Socioeconomic disparities were also evident. Patients earning less than ≥50,000 experienced a five-year overall survival increase from 28.2% pre-2015 to 30.4% post-2015 in regional stages, compared to 35.4% to 38.9% for those earning above ≥100,000. However, in distant stages, survival gains for low-income patients were less pronounced, rising only from 4.5% pre-2015 to 5.2% post-2015, compared to 7.8% to 9.3% for higher-income patients. Younger patients (\u3c35 years) had consistently better outcomes across all stages and periods, with a five-year overall survival of 40.3% pre-2015 and 43.7% post-2015 in distant stages. Conversely, patients aged 50-64 years experienced the lowest survival gains, emphasizing the need for targeted interventions in this group. These findings underscore persistent disparities in NSCLC survival by race and income, despite overall improvements in outcomes over time. Conclusions: While survival improved modestly for NSCLC patients post-2015, significant disparities persist based on stage, race, income, and age. Non-Hispanic Black patients and lower-income individuals face the greatest challenges, underscoring the need for targeted interventions to address these inequities
Sociodemographic disparities in survival outcomes among adolescent and young adult patients with pancreatic cancer: Insights from a SEER database analysis
No full textBackground: Pancreatic cancer in adolescent and young adult (AYA) patients is rare and understudied. Disparities in survival outcomes based on demographic and clinical factors in this population remain poorly understood. This study evaluates survival outcomes and their association with race, gender, stage at diagnosis, and geographic region within a cohort of AYA pancreatic cancer patients. Methods: A retrospective cohort of 2,260 AYA patients (ages 18-39) diagnosed with pancreatic cancer was analyzed. Survival outcomes were assessed using Kaplan-Meier survival analysis and Cox proportional hazards regression to examine the effects of race (American Indian, Asian, Black, White), gender, stage at diagnosis (localized, regional, distant), and geographic region (metropolitan vs. nonmetropolitan). Hazard ratios (HR) with 95% confidence intervals (CI) were calculated to evaluate the impact of these variables on survival, statistical significance was set at P , .05. The median follow-up time was 60 months. Results: The study population comprised of 1,218 females (53.9%) and 1,042 males (46.1%), with a racial distribution of 1,665 White (73.7%), 305 Black (13.5%), 601 Asian (11.8%), and 24 American Indian (1.0%) patients. Males had a higher risk of death compared to females (HR = 1.45;95%CI: 1.28-1.64; p,0.001). Patients in metropolitan areas (n = 2059) had longer median survival (60 months) compared to nonmetropolitan regions (n = 201, median survival = 24 months; p = 0.003). Those with metastatic disease had significantly poorer survival (HR: 17.86; 95% CI: 13.70-23.26, p \u3c .001) compared to patients with localized disease. Racial differences in survival were modest (p = 0.014), with Asian patients showing the highest mean survival (38.4 months) and American Indian patients the lowest (29.9 months). Conclusions: This study demonstrates significant survival disparities among AYA pancreatic cancer patients, with outcomes influenced by stage at diagnosis, gender, race, and geographic region. The findings highlight the importance for targeted interventions to improve outcomes for at-risk groups, including male patients, those with late-stage disease, and individuals in nonmetropolitan regions
Efficacy and safety of pralsetinib in patients with advanced RET-fusion-positive NSCLC: Final data from the phase 1/2 ARROW study
No full textBackground: RET fusions are targetable oncogenic drivers in 1-2% of non-small cell lung cancers (NSCLC). ARROW (NCT03037385) study results (final data lock May 20, 2024) supported the US FDA approval of pralsetinib, a highly potent, oral, selective RET inhibitor for metastatic RET-altered NSCLC. Here, we present final study results. Methods: ARROW was a phase 1/2 open-label study conducted at 84 sites in 13 countries. Phase 2 included patients with RET-fusion-positive NSCLC who received 400 mg pralsetinib once daily (QD). Initially, treatment-naïve patients were not candidates for platinum-based therapy and presented with several unfavorable prognostic factors; this requirement was removed by protocol amendment in July 2019. Primary objectives were overall response rate (ORR, per RECIST v1.1) and safety. Progression-free survival (PFS) and overall survival (OS) are reported in the full efficacy population; the measurable disease population (MDP) was the primary analysis population for ORR and duration of response (DOR). Results: 281 patients with RET-fusion-positive NSCLC received pralsetinib 400 mg QD, with a median duration of treatment of 14.95 months (mos). Median age was 60 years; 46% were male. In the MDP (n=259), ORR was 70.3% (95% confidence intervals [CI]: 64.3, 75.8) and median DOR was 19.1 mos (95% CI: 14.5, 27.9; Table). In the efficacy population (N=281), median OS was 44.3 mos (95% CI: 30.9, 53.1) with median follow up of 47.6 mos (95% CI: 44.8, 49.2), and median PFS was 13.1 mos (95% CI: 11.4, 16.8). ORR (Table) and median PFS were markedly higher in the US (25.9 mos, n=64) vs. Asia (12.6 mos, n=122) or Europe (12.9 mos, n=95). In the safety population, 95% of patients experienced treatment-related adverse events (TRAEs); 66% experienced ≥grade 3. Common TRAEs included increased AST (n=128 [46%]), anemia (n=121 [43%]), increased ALT (n=98 [35%]), and hypertension (n=77 [27%]). 3 patients died due to TRAEs (pneumonia, n=2; interstitial lung disease and rhabdomyolysis, n=1 each). No new safety signals were identified with this update. Conclusions: Pralsetinib produced clinically meaningful and durable responses in patients with RET-fusion-positive NSCLC (regardless of prior therapies) with a manageable safety profile, confirming with this longer follow up previously published results
Amivantamab Plus Lazertinib vs Osimertinib in First-line EGFR-mutant Advanced NSCLC: Longer Follow-up of the MARIPOSA Study
No full textIntroduction: Amivantamab (ami) is an EGFR-MET bispecific antibody with immune cell-directing activity. Lazertinib (laz) is a CNS-penetrant 3rd-generation EGFR TKI. In the primary analysis of the phase 3 MARIPOSA study (NCT04487080), at a median follow-up of 22.0 months, ami plus laz significantly improved progression-free survival (PFS) by blinded independent central review vs osimertinib (osi) in patients with treatment-naïve, EGFR-mutated advanced NSCLC (HR, 0.70; 95 % CI, 0.58-0.85; P \u3c 0.001). Early interim overall survival (OS) analysis showed a favorable trend for ami-laz over osi (HR, 0.80; 95 % CI, 0.61-1.05; P = 0.11). Here, we present updated results with longer follow-up from MARIPOSA. Methods: MARIPOSA randomized 1074 patients with treatment-naïve, EGFRmutated (Exon 19 del or Exon 21 L858R substitutions) locally advanced or metastatic NSCLC 2:2:1 to open-label ami-laz (n = 429), blinded osi (n = 429), or blinded laz (n = 216). This analysis, requested by health authorities, compares ami-laz with osi. Results: At a median follow-upof 31.1 months, 44 % (185/421) and 34 % (145/428) of patients were still on treatment in the ami-laz and osi arms, respectively. In total, 155 patients in the ami-laz arm and 233 in the osi arm had investigator-assessed progressive disease and discontinued treatment. Of those, 72 % (111/155) and 74 % (173/233) initiated subsequent therapy, respectively, with carbo-pem being the most common first subsequent therapy across arms (ami-laz, 26 % [29/111]; osi, 28 % [48/173]). PFS after first subsequent therapy (PFS2) favored ami-laz (HR, 0.73; 95 % CI, 0.59-0.91; nominal P = 0.004). Patients receiving ami-laz demonstrated significantly longer median time to treatment discontinuation and time to subsequent therapy vs osi. Intracranial PFS showed a favorable trend for ami-laz vs osi . While not formally tested for significance, median OS was not estimable for ami-laz vs 37.3 months for osi (HR, 0.77; 95 % CI, 0.61-0.96; nominal P = 0.019). At 24 months, 75 % and 70 % of patients were alive in the ami-laz and osi arms, respectively; corresponding values at 36 months were 61 % and 53 %. Conclusions: Ami-laz continues to show a trend towards improved OS while also improving post-progression outcomes vs osi, reaffirming ami-laz as a firstline standard-of-care for EGFR-mutated advanced NSCLC
Impact of UGT1A1∗28 polymorphism on tolerability in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) treated with NALIRIFOX in NAPOLI 3
No full textBackground: SN-38, the active metabolite of irinotecan, is cleared by the liver enzyme uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) and biliary excretion. UGT1A1∗28 (genotype 7/7) homozygosity is associated with reduced activity of UGT1A1 and a recommendation for dose adjustment of non-liposomal irinotecan, a component of the FOLFIRINOX regimen. In this post-hoc analysis, we analyzed the impact of UGT1A1∗28 homozygosity on the incidence and profile of treatment-emergent adverse events (TEAEs) among patients enrolled in NAPOLI 3 (NCT04083235). Methods: Patients (N = 770) with confirmed untreated mPDAC were randomized (1:1) to receive liposomal irinotecan 50 mg/m2 + oxaliplatin 60 mg/m2 + leucovorin 400 mg/m2 + 5-fluorouracil 2400 mg/m2 (NALIRIFOX) on days 1 and 15 of a 28-day cycle or nab-paclitaxel 125 mg/m2 and gemcitabine 1000 mg/m2 (Gem+NabP) on days 1, 8 and 15 of a 28-day cycle. UGT1A1∗28 status was evaluated in all patients before enrollment. All patients, regardless of UGT1A1∗28 status, received the full starting dose of liposomal irinotecan and followed the same dose reduction rules. This exploratory analysis of TEAEs by UGT1A1∗28 status was descriptive; statistical analyses were not performed. Results: Overall, 83 patients (11.0%) were homozygous for UGT1A1∗28, among whom the incidence of TEAEs was similar to patients with non-homozygous status (Table). The most frequently reported TEAEs (≥ 40%) among the homozygous group (vs the overall NAPOLI 3 population) were diarrhea (59.0% vs 70.5%), nausea (56.4% vs 59.5%), vomiting (46.2% vs 39.7%) and anemia (41.0% vs 26.2%) in the NALIRIFOX arm and nausea (45.5% vs 42.7%), fatigue (45.5% vs 37.7%), diarrhea (45.5% vs 36.7%) and anemia (40.9% vs 40.4%) in the Gem+NabP arm. Conclusions: The incidence of TEAEs, including TEAEs leading to death, was similar between patients with homozygous and non-homozygous UGT1A1∗28 status, in both treatment arms. The profile of TEAEs was consistent with that of the overall NAPOLI 3 population. UGT1A1∗28 status did not substantially influence the safety profile or subsequent need for dose reductions of liposomal irinotecan in NAPOLI 3. (Table Presented)
Anesthesiology Milestones 1.0: Residents\u27 Learning Trajectories and Training Outcomes
No full textBACKGROUND: The Accreditation Council for Graduate Medical Education (ACGME) requires anesthesiology training programs to submit Milestones ratings for each resident every 6 months, starting in the 2014 to 2015 academic year. We aimed to understand how anesthesiology residents progress through the Milestones evaluations from residency entry to graduation.
METHODS: Anesthesiology Milestones 1.0 included 25 subcompetencies in 6 core competencies of Patient Care, Medical Knowledge, Systems-Based Practice, Practice-Based Learning & Improvement, Professionalism, and Interpersonal & Communication Skills. Milestones data from all anesthesiology residency programs from July 2015 to June 2019 were used to (1) assess the prevalence of straight-lining (ie, percentage of residents who received the same rating for all 25 subcompetencies for each program per reporting period), (2) describe residents\u27 progression trajectories in each subcompetency, including the baseline at 6-month training, growth rate (ie, rate increase every 12 months), and outcomes on graduation (ie, percentage of residency graduates who received at least 1 Level 4 [target for graduation] or above subcompetency rating, and percentage of graduates who did not reach Level 4 for at least 1 subcompetency), and (3) use 3-level linear mixed-effect models to examine individual resident growth in each subcompetency over time while accounting for clustering effect of residency programs.
RESULTS: The analyses included 11,691 residents from 153 training programs. Among 6696 clinical anesthesia year 3 residents, 98.3% received at least 1 Level 4 or above rating on graduation; 28.8% to 36.8% of the graduating cohort did not reach Level 4 for at least 1 subcompetency among the 6 core competencies. One hundred and thirty-six programs (88.9% of 153) had straight-lining for at least 1 reporting period. For the multilevel linear mixed-effect models, the fixed intercept estimates were close to 1.0 for Professionalism and Interpersonal & Communication Skills subcompetencies while those for Patient Care subcompetencies were \u3c 0.75; the fixed slope estimates were near 1.0 for all 25 subcompetencies. Across all subcompetencies, residency programs accounted for 63% to 84% of between-resident variability in the baseline ratings and 60% to 92% of between-resident variability in the growth rates.
CONCLUSIONS: We found a high prevalence of straight-lining in Anesthesiology Milestones 1.0 ratings. This raises concerns about whether Milestones evaluations reflect individual resident performance in specific domains. The programs explained most of the between-resident variability in both baseline ratings and growth rates. Future studies are needed to promote standardization and consistency of Milestones evaluations, allowing learners to track their progress and target specific areas to improve performance
HEAL together : a randomized, hybrid type 1 effectiveness-implementation trial protocol of a peer-delivered behavioral activation intervention to improve methadone treatment retention
No full textBACKGROUND: Although medications exist to effectively treat opioid use disorder (OUD), treatment retention is a pressing challenge. Peer recovery specialists (PRSs) may play an important role in OUD treatment retention, yet few evidence-based interventions to support OUD retention have been developed specifically for PRS delivery. Behavioral activation is a brief, reinforcement-based intervention with empirical support for improving depression and substance use outcomes, delivered typically by specialist mental health providers. Informed by key stakeholder feedback, our team adapted a behavioral activation and problem-solving intervention for PRS delivery (
METHODS: The trial is being conducted at a large methadone treatment program in Baltimore City, Maryland. We are enrolling 200 patients who recently initiated methadone treatment or are experiencing challenges with methadone adherence in a randomized 1:1 ratio to receive
DISCUSSION: This trial will provide insight as to whether a PRS-delivered intervention may be effective and feasible for improving methadone treatment retention and other behavioral health outcomes. If findings are promising,
CLINICAL TRIAL REGISTRATION: NCT05299515
