Binary Endpoints Research Articles

Comparative Efficacy of Ciltacabtagene Autoleucel Versus Elotuzumab, Isatuximab, and Selinexor-Based Regimens in the Treatment of Patients with Relapsed or Refractory Multiple Myeloma with 1-3 Prior Lines of Therapy Using a Matching-Adjusted Indirect Comparison

Introduction: Ciltacabtagene autoleucel (cilta-cel; Carvykti) was assessed in the phase 3 randomized controlled trial CARTITUDE-4 for adult patients with relapsed and refractory multiple myeloma (RRMM) who have received 1-3 prior line(s) of therapy (LOT) that included an immunomodulatory agent (IMiD), and a proteasome inhibitor (PI) and are refractory to lenalidomide. Other therapies used to treat patients with multiple myeloma who have received at least one other therapy and are lenalidomide-refractory vary by country, but broadly include doublet and triplet regimens based on daratumumab, pomalidomide, bortezomib, and carfilzomib. This analysis aims to compare efficacy outcomes in patients randomized to the cilta-cel arm of CARTITUDE-4 versus relevant comparators based on their target trial populations. Methods: Comparators for the matching adjusted indirect comparisons (MAICs) were identified a priori based on regimens used in the target population including; SVd, EloPd, IsaKd, DKd, DVd, Kd, Vd, Pd, and Ide-cel. PVd and DPd were not of interest given their inclusion in the CARTITUDE-4 trial. Melflufen+d, PanVd, VenVd, PCd, IxaKd, D-monotherapy, V-monotherapy, CyVd, and DVCd were not of interest for the US, EU-5, the Netherlands, and Canada. A systematic literature review identified publications of relevant clinical trials for these treatments, which were assessed for feasibility of an indirect treatment comparison. Feasibility was determined based on study design and degree of overlap with the CARTITUDE-4 population (prior LOT, lenalidomide-refractoriness, and exclusion criteria around previous therapies, i.e., prior daratumumab). We report here on comparisons vs. EloPd (ELOQUENT-3), IsaPd (ICARIA-MM), and SVd (BOSTON). Due to differences in methods for the comparisons versus ide-cel (KarMMa-3) and versus DKd, Kd, DVd, Vd, and Pd, these are reported separately. Comparison to IsaKd was not feasible due to a lack of published data in the lenalidomide-refractory subgroup (baseline characteristics and efficacy data), and key differences in exclusion criteria. Given the lack of a common comparator between CARTITUDE-4 and the comparator trials, unanchored MAICs were performed utilizing individual patient-level data (IPD) from patients randomized to the cilta-cel arm of CARTITUDE-4 (N=208). The eligibility criteria from each of the comparator trials were applied to the cilta-cel IPD, and outcomes for the matched population were compared against published summary data for EloPd (N=60), IsaPd (N=154), and SVd (N=195) using reconstructed IPD for response endpoints and simulated IPD from published Kaplan-Meier (KM) curves for progression-free survival (PFS). Further imbalances in patient characteristics were adjusted by weighting the cilta-cel data to match the reported baseline characteristics of the comparator trials in terms of refractory status, cytogenetic risk, ISS stage, and presence of extramedullary disease. Comparative efficacy was estimated for overall response rate (ORR), very good partial response or better (≥VGPR) rate, complete response or better (≥CR) rate, and PFS. For binary endpoints, relative effects were quantified using relative response ratios (RRs) with 95% confidence intervals (CIs) derived from a weighted logistic regression analysis. For PFS, HRs including 95% CIs were estimated using a weighted Cox proportional hazards model. Results: After adjustment, patients in the cilta-cel arm were significantly more likely to achieve an overall response than patients in EloPd or IsaPd arms, and to achieve ≥VGPR and ≥CR versus patients in all other comparators arms ( Table 1). In addition, cilta-cel was associated with a significant reduction in the risk of disease progression or death (PFS) versus all comparators, ranging from 39% (versus SVd) to 68% (versus IsaPd) ( Table 2). Conclusions: Cilta-cel demonstrated clinical benefit over EloPd, IsaPd, and SVd for response outcomes and PFS, highlighting its potential as an effective treatment option for patients with RRMM who have received at least one other therapy and are lenalidomide-refractory. These comparisons provide valuable information to contextualize the efficacy of cilta-cel in countries where treatment for these patients may be different from DPd or PVd.

A Matching-Adjusted Indirect Comparison of the Efficacy of Elranatamab Versus Physician's Choice of Treatment in Patients with Triple-Class Exposed/Refractory Multiple Myeloma

BACKGROUND For patients with triple-class exposed/refractory multiple myeloma (TCE/R MM), prognosis is poor and limited effective treatment options are available. Elranatamab is a novel B-cell maturation antigen (BCMA)- and CD3-directed bispecific antibody that demonstrated safety and efficacy in patients with TCE/R MM in the phase 2, single-arm MagnetisMM-3 trial (NCT04649359). To compare the effectiveness of elranatamab vs physician's choice of treatment (PCT) in the absence of comparative data, an unanchored matching-adjusted indirect comparison (MAIC) was conducted. METHODS Individual patient data (IPD) from the 14.7-month follow-up of MagnetisMM-3 (Cohort A [BCMA-naïve] N=123) was matched to published summary data from two real-world studies of PCT: LocoMMotion ([NCT04035226]), an ongoing, prospective, non-interventional study of PCT in patients with TCE MM (N=248); and MAMMOTH, a multicenter, retrospective study investigating the history and outcomes of patients with TCE MM who received subsequent therapies (N=177). To adjust for differences in baseline characteristics, patients from MagnetisMM-3 were reweighted to match those in LocoMMotion reported in Mateos et al (2022) and MAMMOTH reported in Bal et al (2022). The base-case adjustment variables were selected based on univariate Cox regressions using the MagnetisMM-3 IPD, a systematic literature review of prognostic variables and effect modifiers in RRMM, a review of the prognostic variables identified in clinical studies for TCE/R MM, a review of the recent analogous indirect comparisons, and confirmation by clinical experts. Weights were determined using a propensity score-type logistic regression via the method of moments (Signorovitch et al. 2012) based on age, median time since diagnosis, International Staging System disease stage, high-risk cytogenetics, extramedullary disease, number of prior lines of therapy, Eastern Cooperative Oncology Group performance status, creatinine clearance, and penta-exposed and penta-refractory status (where available). In the analysis for the endpoint of overall survival (OS), sex was also included in the analysis. A sensitivity analysis was conducted in which missing values of the adjusted baseline characteristics for elranatamab were imputed by a random sample of the observations in MagnetisMM-3 to potentially increase the effective sample size (ESS). Unanchored MAIC analyses used the R Studio statistical code provided in the National Institute for Health and Care Excellence Decision Support Unit 18 by Phillippo et al (2016) . In the MAIC vs LocoMMotion & MAMMOTH, adjusted objective response rate (ORR), complete response rate or better (≥CR), progression-free survival (PFS), and OS at 15 months for elranatamab were compared with PCT. Results were reported as rate differences, which is the difference between the ORR or ≥CR rates of elranatamab and PCT, and odds ratios (ORs) for binary endpoints and hazard ratios (HRs) for time-to-event endpoints, with two-sided 95% confidence intervals (CIs). RESULTS In the MAIC for elranatamab vs PCT in LocoMMotion, the post-matching ESS was 68 for all endpoints in the base case. Compared with PCT in LocoMMotion, elranatamab was associated with a significantly higher ORR (rate difference: 37.52; 95% CI 26.20-48.83; OR: 4.85; 95% CI 2.85-8.23), higher ≥CR (rate difference: 42.29; 95% CI 31.84-52.74; OR: 184.01; 95% CI 24.66-1372.86), and longer PFS (HR 0.32; 95% CI 0.20-0.49) and OS (HR 0.62; 95% CI 0.40-0.94) (Table 1). In the MAIC vs PCT in MAMMOTH, the base-case post-matching ESSs were 100 for all endpoints. Compared with PCT in MAMMOTH, elranatamab was associated with a significantly higher ORR (rate difference: 28.14; 95% CI 16.77-39.52; OR: 3.24; 95% CI 1.98-5.32) and ≥CR (rate difference: 26.22; 95% CI 16.40-36.05; OR: 5.48; 95% CI 2.88-10.44). Elranatamab also had longer PFS (HR 0.25; 95% CI 0.17-0.37) and OS (HR 0.49; 95% CI 0.33-0.71) than PCT (Table 2). Sensitivity analysis results were consistent with the base case. CONCLUSIONS In this MAIC, elranatamab demonstrated significantly higher ORR, higher ≥CR rate, longer PFS, and longer OS compared with PCT in the real-world. These results suggest that elranatamab offers significantly improved outcomes versus standard treatments used in patients with TCE/R MM in clinical practice.

Efficacy of Vitamin C with Iron Supplementation in Iron Deficiency Anemia Patients: A Systematic Review and Meta-Analysis

Background Oral iron supplementation is one of the mainstays of treatment for iron deficiency anemia (IDA) but can be complicated by poor absorption. Vitamin C is hypothesized to increase the acidity of the GI tract and enhance the conversion of non-absorbable ferric iron (Fe 3+) to its absorbable ferrous (Fe 2+) state for improved absorption and is often prescribed with iron. However, whether vitamin C supplementation translates to clinically relevant differences, such as sufficient improvements in hemoglobin, remains unclear and a synthesis of available evidence is lacking. Therefore, the present systematic review and meta-analysis aims to compare oral iron with or without vitamin C supplementation in patients with IDA. Methods MEDLINE, EMBASE, Web of Science and Cochrane Central Register of Controlled Trials were searched from database inception to July 2023 for randomized controlled trials (RCTs) and non-randomized studies (NRSs) that investigated the use of oral iron supplements with vitamin C compared to oral iron supplements only in patients with IDA. Title & abstract, full text review and data extraction were conducted independently and in duplicate. The primary outcome was the change in serum hemoglobin levels in g/dL. Secondary outcomes include change in serum ferritin, change in transferrin saturation, change in reticulocyte percentage, and incidence of adverse events including constipation, nausea/vomiting, GI upset and poor taste. The Mantel-Haenszel fixed effects model was utilized for the meta-analysis. The calculated effect sizes were represented by odds ratios (OR) and mean differences (MD) for binary endpoints and continuous endpoints, respectively, with 95% confidence intervals (CI). Results 2231 studies were retrieved from electronic databases. 12 RCTs and one prospective cohort study comprising 2240 patients were included. There was a small but statistically significant increase in serum hemoglobin level (MD 0.14 g/dL [95%CI 0.08, 0.20]) and serum ferritin levels (MD 3.23 µg/L [95%CI 1.63, 4.84]) in the iron + vitamin C group compared to the iron only group. There was a greater reduction in serum transferrin saturation associated with vitamin C supplementation (MD -2.01% [95%CI -3.31, -0.71%]) but the pool of evidence consists of only two studies. Reticulocyte percentage (MD 0.22% [95%CI 0.08, 0.36]) was higher in the iron + vitamin C group than in the iron only group. There were no significant differences between the iron + vitamin C group and the iron only group in overall incidence of adverse effects (OR 0.71 [95%CI 0.50, 1.00]), constipation (odds ratio (OR) 0.83 [95%CI 0.35, 1.96]), or nausea/vomiting (OR 0.80 [95%CI 0.52, 1.24]). The risk of GI upset is lower in the iron + vitamin C group (OR 0.40 [95%CI 0.18, 0.92]). Nevertheless, only three primary studies reported on incidence of adverse events. Conclusion The addition of vitamin C to iron supplementation in the management of IDA was associated with a statistically significant, but likely clinically unimportant, increase in serum hemoglobin of 0.14 g/dL. Similarly, a statistically significant increase in serum ferritin levels by 3.23 µg/L was observed, but its clinical relevance remains uncertain. A strength of the present analysis is the number of RCTs included; however, its conclusions are limited by the heterogeneity of interventions (e.g. different formulations/dosage) across studies. Our results do not provide strong evidence for adding vitamin C to iron supplementation.

A Matching-Adjusted Indirect Comparison of the Efficacy of Elranatamab and Teclistamab in Patients with Triple-Class Exposed/Refractory Multiple Myeloma

BACKGROUND Elranatamab, a novel B-cell maturation antigen (BCMA)- and CD3-directed bispecific antibody, recently demonstrated efficacy and safety in patients with triple-class exposed/refractory multiple myeloma (TCE/R MM) in the phase 2, single-arm MagnetisMM-3 trial (NCT04649359). Teclistamab (TEC) is a BCMA-CD3 directed bispecific antibody which was recently approved in the US for patients with TCE/R MM who received 4+ prior lines of treatment, based on response rates in the MajecTEC-1 trial (NCT04557098). In the absence of comparative trials of elranatamab and TEC, an unanchored matching-adjusted indirect comparison (MAIC) was conducted to assess their relative efficacy. METHODS Individual patient data (IPD) from the 14.7 month follow- up of MagnetisMM-3 Cohort A (BCMA-naïve, N = 123), were reweighted to match published summary data from ~23 month follow-up in MajesTEC-1 (N=165) in Sidana et al (2023). Overall, the inclusion and exclusion criteria of the trials were similar; however, MajesTEC-1 excluded patients with Eastern Cooperative Oncology Group (ECOG) performance status >1; therefore, patients with ECOG 2 in the MagnetisMM-3 trial were removed from the analysis (resulting N=116). To adjust for cross-trial differences, patients from MagnetisMM-3 were reweighted to match the baseline characteristics of the TEC trial patients. Weights were determined using a propensity score-type logistic regression via the method of moments (Signorovitch et al. 2012) based on age, median time since diagnosis, International Staging System disease stage, high-risk cytogenetics, extramedullary disease, number of prior lines of therapy, ECOG performance status, and penta-exposed and penta-refractory status. In the analysis for the overall survival (OS) endpoint, sex was also included. The adjusted variables were obtained based on univariate Cox regressions using the MagnetisMM-3 IPD, a systematic literature review of prognostic variables and effect modifiers in relapsed or refractory MM, a review of the prognostic variables identified in clinical studies for TCE/R MM, and a review of the recent relevant indirect comparisons, and were confirmed by clinical experts. A sensitivity analysis was conducted in which missing values of the adjusted baseline characteristics for elranatamab were imputed by a random sample of the observations in MagnetisMM-3 to potentially increase the effective sample size (ESS). Unanchored MAIC analyses were conducted in R studio following the code provided in the National Institute for Health and Care Excellence (NICE) Decision Support Unit (DSU) 18 by Phillippo et al (2016). The efficacy outcomes included objective response rate (ORR), duration of response (DoR), progression-free survival (PFS), and OS. Kaplan-Meier curves of DoR, PFS, and OS from MajesTEC-1 were digitized according to Guyot et al (2012). Results were reported as rate difference (i.e., the difference between the ORR of elranatamab and TEC) and odds ratios (ORs) for binary endpoints or hazard ratios (HRs) for time-to-event endpoints, with 95% confidence intervals (CIs). RESULTS After adjustment in the MAIC, the selected key baseline characteristics were comparable between elranatamab and TEC. For all endpoints except OS, the post-matching ESS for elranatamab was 75 in the base case and 89 in the sensitivity analysis. For OS, the ESSs were 73 and 87 for the base case and scenario analyses, respectively. Compared with TEC, elranatamab was associated with significantly better ORR (rate difference: 12.30; 95% CI: 0.70-23.90; OR: 1.79; 95% CI: 1.01-3.19) and PFS (HR 0.59; 95% CI 0.39-0.89). Patients treated with elranatamab had numerically better DoR (HR: 0.64; 95% CI: 0.33-1.23) and OS (HR: 0.66; 95% CI: 0.42-1.03) compared to those who received TEC (Table 1 and 2). Results in the sensitivity analysis were consistent with the base case. CONCLUSIONS In this MAIC, elranatamab demonstrated significantly better ORR and PFS than TEC, and numerically better DOR and OS in both the base case and the sensitivity analysis. These results suggest that elranatamab is an effective option for treating patients with TCE/R MM.

Effect of Mavacamten in Women Compared With Men With Obstructive Hypertrophic Cardiomyopathy: Insights From EXPLORER-HCM.

Compared with men, women with hypertrophic cardiomyopathy (HCM) have a higher incidence of heart failure and worse outcomes. We investigated baseline clinical and echocardiographic characteristics and response to mavacamten among women compared with men in the EXPLORER-HCM study (Clinical Study to Evaluate Mavacamten [MYK-461] in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy). A prespecified post hoc analysis of sex from the blinded, randomized EXPLORER-HCM trial of mavacamten versus placebo in symptomatic patients with obstructive HCM was performed. Baseline characteristics were compared with t tests for continuous variables (expressed as mean values) and χ2 tests for categorical variables. Prespecified primary, secondary, and exploratory end points and echocardiographic measurements from baseline to end of treatment (week 30) were analyzed with ANCOVA for continuous end points and a generalized linear model with binomial distribution for binary end points, with adjustment for each outcome's baseline value, New York Heart Association class, β-blocker use, and ergometer type. At baseline, women (n=102) were older (62 years versus 56 years; P<0.0001), had lower peak oxygen consumption (16.7 mL·kg-1·min-1 versus 21.3 mL·kg-1·min-1; P<0.0001), were more likely to be assigned New York Heart Association class III (42% versus 17%; P<0.0001), had worse health status (Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score 64 versus 75; P<0.0001), and had higher baseline plasma NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels (1704 ng/L versus 990 ng/L; P=0.004) than men (n=149). After 30 weeks of mavacamten treatment, similar improvements were observed in women and men in the primary composite end point (percentage difference on mavacamten versus placebo, 22% versus 19%, respectively; P=0.759) and in the secondary end points of change in postexercise left ventricular outflow tract gradient (-42.4 mm Hg versus -33.6 mm Hg; P=0.348), change in peak oxygen consumption (1.2 mL·kg-1·min-1 versus 1.6 mL·kg-1·min-1; P=0.633), and percentage achieving ≥1 New York Heart Association class improvement (41% versus 28%; P=0.254). However, women had greater improvement in health status (Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score 14.8 versus 6.1; P=0.026) and in the exploratory end point of NT-proBNP levels (-1322 ng/L versus -649 ng/L; P=0.0008). Although at baseline women with symptomatic obstructive HCM enrolled in EXPLORER-HCM were older and had worse heart failure and health status than men, treatment with mavacamten resulted in similar improvements in the primary and most secondary EXPLORER-HCM end points and greater improvements in health status and NT-proBNP. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03470545.

CTNI-16. USE OF PREDICTIVE SCORE-BASED HISTORICAL CONTROL DATA IN SINGLE-ARM TRIALS

Abstract Even though the randomized controlled trials (RCTs) are still the preferred approach to evaluate the effects of treatments, single-arm study designs have been traditionally used in Phase II oncology clinical trials. The single-arm studies using historical control or external control might be inevitable and even fatal when concurrent controls are impractical or unethical in rare and high-risk diseases. Due to recruiting difficulty, ethical and economic reasons, the single-arm trials can be a good option to test the experimental efficacy with the external control data of historical control rates for early efficacy phase 2 trials in glioblastoma. The FDA guidelines on external control data focus on the use of patient-level data from other clinical trials or real-world data (RWD), and so there is no guidance for summary-level historical control. Furthermore, there exist methodological issues to use historical data like identification of relevant data, amount of discounting (time difference and dissimilarity), prior robustness or operating characteristics. In this study, we propose a synthetic data based predictive scoring method optimally to match the historical control data with the characteristic conditions of the experimental studies. We consider both a binary (PFS on six months) and survival (median PFS) endpoints as surrogates for Phase 2 single-arm trials in newly diagnosed and recurrent glioblastoma patients. We perform meta-analysis to summarize the endpoints and the related socio-demographic, treatment and genetic factors from the summary-level historical data. Then we generate the synthetic patients based on the meta-summarized data. The generalized boosted regression models will be used to identify significant characteristics affecting the survival of GBM patients using the synthetic data. Finally the predictive score-based historical data model will be developed to provide the optimal matching with the characteristics of the experimental studies. This study will be validated using existing patient-level data as well as cross-validation methods.

Abstract 14450: Effects of SGLT2 Inhibitors in Patients With Acute Myocardial Infarction Undergoing Percutaneous Coronary Intervention: A Meta-Analysis of Randomized Controlled Trials

Background: Sodium-glucose co-transporter-2 inhibitors (SGLT2i) are a class of drugs initially developed for the treatment of type 2 diabetes mellitus which demonstrated benefits in reducing cardiovascular complications. However, the benefits of using SGLT2i after acute myocardial infarction (AMI) still have limited evidence. Research Questions: Does the use of SGLT2i after percutaneous coronary intervention (PCI) due to AMI contribute to reducing mortality and hospitalization due heart failure (HF)? Aims: To assess the benefit of SGLT2i after AMI in patients undergoing PCI in reducing overall mortality, cardiovascular mortality and occurrence of HF. Methods: PubMed, Scopus, Cochrane Library and Web of science databases were searched for randomized controlled trials (RCTs) comparing SGLT2i with placebo after AMI in patients undergoing PCI. We computed risk ratios (RRs) for binary endpoints, with 95% confidence intervals (CIs). The heterogeneity was evaluated with I 2 statistics. R Software, version 4.2.1, was used for statistical analysis. The protocol was registered in PROSPERO (CRD42023424657). Results: A total of 4 RCTs with 1,311 patients, of whom 439 (33.48%) underwent SGLT2i therapy. The mean age was 60.2 (10.9) years in the SGLT2i group and 66.5 (13.8) years in the placebo group. Mean follow-up ranged from 23 to 96 weeks. In the pooled analysis, SGLT2i significantly reduced hospitalization due to HF (RR 0.39; 95% CI 0.20-0.75; p&amp;lt;0.01; I 2 =0%). There were no significant differences between SGLT2i and placebo regarding cardiovascular death (RR 0.52; 95% CI 0.23-1.18; p=0.12; I 2 =20%), non-cardiovascular death (RR 0.79; 95% CI 0.26-2.38; p=0.68; I 2 =0%) and all- cause death (RR 0.59; 95% CI 0.30-1.13; p=0.11; I 2 =12%). Conclusion(s): SGLT2i were associated with a reduction in hospitalization due to HF. However, no differences were found for cardiovascular, non-cardiovascular or all-cause deaths.

Greater time spent with HbA1c less than 7.0% with oral semaglutide versus oral comparators: An exploratory analysis of the PIONEER studies.

To assess how long participants with type 2 diabetes spent with HbA1c less than 7.0% and how likely they were to maintain this targetwith oral semaglutide 7 mg versus sitagliptin 100 mg or oral semaglutide 14 mg versus empagliflozin 25 mg, sitagliptin 100 mg or subcutaneous liraglutide 1.8 mg. Analyses used on-treatment data without rescue medication for all randomized participants (semaglutide [approved maintenance doses], n = 1880; comparators [not including placebo], n = 1412). Duration of time with HbA1c less than 7.0% was calculated using an HbA1c time curve. A binary endpoint of achieving HbA1c less than 7.0% at weeks 26 (week 24 for PIONEER 7) and 52 of each trial (and week 78 for PIONEER 3) was analysed. Mean duration of time with HbA1c less than 7.0% was greater with oral semaglutide 7 mg versus sitagliptin in PIONEER 3 (27 vs. 22 weeks) and with oral semaglutide 14 mg versus empagliflozin and sitagliptin (27-34 vs. 19 vs. 22 weeks, respectively), and similar versus subcutaneous liraglutide. A greater proportion of participants achieved and maintained HbA1c less than 7.0% for more than 75% of the trial with oral semaglutide 14 mg versus oral comparators. The odds of achieving HbA1c less than 7.0% at weeks 24/26 and 52/78 were significantly greater with oral semaglutide 14 mg versus oral comparators or subcutaneous liraglutide, and with oral semaglutide 7 mg versus sitagliptin. Oral semaglutide 7 and 14 mg resulted in greater time spent with HbA1c less than 7.0%, and a greater likelihood of achieving and maintaining HbA1c less than 7.0% versus oral comparators.

Patient Benefits of Radical Prostatectomy in Certified Prostate Cancer Centers: Comparative Results from the Multicenter IMPROVE Study

Introduction: We investigated differences in treatment outcomes following radical prostatectomy (RP) between certified centers (CCs) and noncertified centers (nCCs) within the IMPROVE study group. Methods: A validated survey assessing various factors, including stress urinary incontinence (SUI) and decision regret (DR), was administered to 950 patients who underwent RP across 19 hospitals (12 CCs and 7 nCCs) at a median follow-up of 15 months after RP (interquartile range: 11–20). The response rate was 74%, with 703 patients participating, including 480 (68%) from CCs. Multivariate binary regression models were used to analyze differences between CCs and nCCs regarding the following binary endpoints: nerve-sparing (NS), positive surgical margins (PSM), SUI (defined as >1 safety pad), complications based on the Clavien-Dindo classification (grade ≥1, grade ≥3) and DR (>15 points indicating critical DR). Results: Considering the multivariate analysis, the rate of NS surgery was lower in CCs than in nCCs (OR = 0.52; p = 0.004). No significant differences were observed in the PSM rate (OR = 1.67; p = 0.051), SUI (OR = 1.03; p = 0.919), and DR (OR = 1.00; p = 0.990). SUI (OR 0.39; p < 0.001) and DR (OR 0.62; p = 0.026) were reported significantly less frequently by patients treated with robotic-assisted RP, which was significantly more often performed in CCs than in nCCs (68.3% vs. 18%; p < 0.001). The total complication rate was 45% lower in CCs (OR = 0.55; p = 0.004), although the number of complications requiring intervention (Clavien-Dindo classification ≥3) did not differ significantly between CCs and nCCs (OR = 2.52; p = 0.051). Conclusion: Within the IMPROVE study group, similarly favorable outcomes after RP were found in both CCs and nCCs, which, however, cannot be transferred to the general treatment landscape of PCA in Germany. Of note, robotic-assisted RP was more often performed in CCs and associated with less SUI and DR, while open prostatectomy was the treatment of choice in low-volume nCCs. Future prospective and region wide studies should also investigate the surgeon caseload and experience as well as a spillover effect of the certification process on nCCs.

Comparative Efficacy of Ciltacabtagene Autoleucel Versus Idecabtagene Vicleucel in the Treatment of Patients with Relapsed or Refractory Multiple Myeloma Previously Treated with 2-4 Prior Lines of Therapy Using a Matching-Adjusted Indirect Comparison

Introduction: Two novel B-cell maturation antigen (BCMA)-targeting chimeric antigen receptor T-cell (CAR-T) therapies, ciltacabtagene autoleucel (cilta-cel; Carvykti) and idecabtagene vicleucel (ide-cel; Abecma), were recently developed and approved in 2022 and 2021, respectively, for heavily pre-treated relapsed/refractory multiple myeloma (RRMM) based on the CARTITUDE-1 and KarMMa studies. A previous comparison of these therapies in triple-class exposed patients demonstrated improved efficacy with cilta-cel versus ide-cel (Martin T, et al. Curr Med Res Opin. 2023;39(1):81-89). More recently, the efficacy and safety of these CAR-Ts were demonstrated earlier in the treatment pathway in lenalidomide-refractory, proteasome inhibitor (PI)-exposed patients with 1-3 prior line(s) of treatment (LOT; cilta-cel; CARTITUDE-4), and in triple-class exposed patients with 2-4 prior LOT (ide-cel; KarMMa-3). In the absence of a head-to-head comparison of these two therapies, an unanchored matching-adjusted indirect comparison (MAIC) was used to estimate their relative efficacy using data from CARTITUDE-4, CARTITUDE-1, and KarMMa-3. Methods: While KarMMa-3 and CARTITUDE-4 both included DPd in the physician's choice control arm, there is no published data on this subgroup from KarMMa-3. As such, an unanchored MAIC was performed utilizing individual patient-level data (IPD) from 245 patients who received cilta-cel; 208 patients from CARTITUDE-4 who had received 1-3 prior LOT and 37 patients from CARTITUDE-1 who had received 3-4 prior LOT. From these data, cilta-cel patients who fulfilled the inclusion criteria from KarMMa-3 (2-4 prior LOT and triple-class exposed) were selected, and their outcomes were compared against published summary data for ide-cel (N=254) from KarMMa-3 using reconstructed IPD for response endpoints and simulated IPD from published Kaplan-Meier (KM) curves for progression-free survival (PFS). Further imbalances in patient characteristics were adjusted for by weighting the cilta-cel IPD to match the reported baseline characteristics of KarMMa-3 in terms of refractory status, ISS stage, time to progression on prior LOT, cytogenetic risk, and presence of extramedullary disease. Comparative efficacy was estimated for overall response rate (ORR), very good partial response or better (≥VGPR) rate, complete response or better (≥CR) rate, and PFS. For binary endpoints, relative effects were quantified using relative response ratios (RRs) with 95% confidence intervals (CIs) derived from a weighted logistic regression analysis. For PFS, the hazard ratio (HR) with 95% CIs for cilta-cel versus ide-cel was estimated using a weighted Cox proportional hazards model. Results: After applying the KarMMa-3 inclusion and exclusion criteria to the CARTITUDE-1 and CARTITUDE-4 IPD (excluding patients with only 1 prior LOT or no prior daratumumab), 36 patients and 49 patients were included from the cilta-cel trials, respectively. After adjustment, patients in the cilta-cel group (effective sample size [ESS]=46) were significantly more likely to achieve an overall response (RR: 1.18 [95% CI: 1.04, 1.33]; p=0.0404), and to reach deeper levels of response as demonstrated by ≥VGPR (RR: 1.34 [95% CI: 1.16, 1.56]; p=0.0027), and ≥CR (RR: 1.91 [95% CI: 1.56, 2.34]; p&amp;lt;0.0001) compared to patients in the ide-cel group ( Table). In addition, a statistically significant reduction of 49% in the risk of disease progression or death was observed with cilta-cel versus ide-cel (HR: 0.51 [95% CI: 0.31, 0.84]; p=0.0078; Figure). Conclusions: This unanchored MAIC showed that cilta-cel provides clinical benefit over ide-cel across response outcomes and PFS for patients with triple-class exposed RRMM treated with 2-4 prior LOT. These results are consistent with the previous comparison in later line, triple-class exposed patients, continuing to highlight the value of cilta-cel for these patients. Furthermore, these comparisons provide valuable information to contextualize the efficacy of cilta-cel compared to other available CAR-Ts for multiple myeloma.

Efficacy of Testosterone Replacement Therapy in Correcting Anemia in Men With Hypogonadism

Testosterone deficiency causes mild anemia. Whether testosterone replacement therapy (TRT) can correct anemia or prevent the development of anemia in men with hypogonadism remains incompletely understood. To assess the efficacy of TRT in correcting anemia in men with hypogonadism and anemia, and reducing the risk of developing anemia in those without anemia. This randomized, placebo-controlled trial included men with hypogonadism at 316 US sites enrolled between May 2018 and February 2022. This study was nested within the Testosterone Replacement Therapy for Assessment of Long-term Vascular Events and Efficacy Response in Hypogonadal Men (TRAVERSE) Study, which evaluated the effect of TRT on major adverse cardiovascular events in middle-aged and older men with hypogonadism. Eligible participants were aged 45 to 80 years, with 2 testosterone concentration results below 300 ng/dL, hypogonadal symptoms, and cardiovascular disease (CVD) or increased CVD risk. The last study visit took place in January 2023. Data were analyzed between March and August 2023. Participants were randomized with stratification for preexisting CVD to 1.62% testosterone gel or placebo gel daily for the study duration. Proportion of participants with anemia (hemoglobin below 12.7 g/dL) whose anemia remitted (hemoglobin 12.7 g/dL or above) over the study duration. Secondary end points included incidence of anemia among men who were not anemic. Binary end points were analyzed using repeated-measures log-binomial regression. A total of 5204 men were included, 815 with anemia (mean [SD] age, 64.8 [7.7] years; 247 Black [30.3%], 544 White [66.7%], 24 other [2.9%]) and 4379 without anemia (mean [SD] age, 63.0 [7.9] years; 629 Black [14.4%], 3603 White [82.3%], 147 other [3.4%]). Anemia corrected in a significantly greater proportion of testosterone-treated than placebo-treated men at 6 months (143 of 349 [41.0%] vs 103 of 375 [27.5%]), 12 months (152 of 338 [45.0%] vs 122 of 360 [33.9%]), 24 months (124 of 290 [42.8%] vs 95 of 307 [30.9%]), 36 months (94 of 216 [43.5%] vs 76 of 229 [33.2%]), and 48 months (41 of 92 [44.6%] vs 38 of 97 [39.2%]) (P = .002). Among participants without anemia, a significantly smaller proportion of testosterone-treated men developed anemia than placebo-treated men. Changes in hemoglobin were associated with changes in energy level. In middle-aged and older men with hypogonadism and anemia, TRT was more efficacious than placebo in correcting anemia. Among men who were not anemic, a smaller proportion of testosterone-treated men developed anemia than placebo-treated men. ClinicalTrials.gov Identifier: NCT03518034.

PD-1/PD-L1 Inhibitors plus Chemotherapy Versus Chemotherapy Alone for Resectable Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: The benefit of adding programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors to the treatment of early-stage non-small cell lung cancer (NSCLC), both neoadjuvant therapy (NAT) and adjuvant therapy (AT), is not yet fully elucidated. Methods: We searched PubMed, Embase, and Cochrane databases for randomized controlled trials (RCT) that investigated PD-1/PD-L1 inhibitors plus chemotherapy for resectable stage NSCLC. We computed hazard ratios (HRs) or odds ratios (ORs) for binary endpoints, with 95% confidence intervals (CIs). Results: A total of seven RCTs comprising 3915 patients with resectable stage NSCLC were randomized to chemotherapy with or without PD-1/PD-L1 inhibitors as NAT or AT. As NAT, the PD-1/PD-L1 inhibitors plus chemotherapy group demonstrated significantly improved overall survival (HR 0.66; 95% CI 0.51-0.86) and event-free survival (HR 0.53; 95% CI 0.43-0.67) compared with the chemotherapy alone group. There was a significant increase in favor of the PD-1/PD-L1 inhibitors plus chemotherapy group for major pathological response (OR 6.40; 95% CI 3.86-10.61) and pathological complete response (OR 8.82; 95% CI 4.51-17.26). Meanwhile, as AT, disease-free survival was significant in favor of the PD-1/PD-L1 inhibitors plus chemotherapy group (HR 0.78; 95% CI 0.69-0.90). Conclusions: In this comprehensive systematic review and meta-analysis of RCTs, the incorporation of PD-1/PD-L1 inhibitors alongside chemotherapy offers a promising prospect for reshaping the established treatment paradigms for patients diagnosed with resectable stages of NSCLC. Moreover, our analyses support that neoadjuvant administration with these agents should be encouraged, in light of the fact that it was associated with an increased survival and pathological response, at the expense of a manageable safety profile.

Mavacamten for Obstructive Hypertrophic Cardiomyopathy With or Without Hypertension: Post-Hoc Analysis of the EXPLORER-HCM Trial

BackgroundHypertension (HTN) is common in patients with hypertrophic cardiomyopathy (HCM), but its effect on the treatment of left ventricular outflow tract (LVOT) obstruction is undefined. Although elevated systolic blood pressure (SBP) may impact dynamic LVOT gradients, its response to cardiac myosin inhibition is unknown. ObjectivesIn a post hoc exploratory analysis of the EXPLORER-HCM trial (Clinical Study to Evaluate Mavacamten [MYK-461] in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy), the authors examined the characteristics of patients with obstructive HCM and HTN and the associations between HTN, SBP, and the response to mavacamten treatment of LVOT obstruction. MethodsPatients were stratified by baseline history of HTN and mean SBP during 30-week treatment with mavacamten or placebo. The study estimated treatment differences and evaluated HTN and SBP groups by treatment interaction. Analysis of covariance was used to model changes in continuous endpoints, and a generalized linear model was used for binary endpoints. ResultsHTN was present in 119 of 251 patients (47.4%), including 60 receiving mavacamten and 59 receiving placebo. Patients with HTN vs no HTN were older (63.4 vs 54.0 years; P < 0.001), had higher SBP (134 ± 15.1 mm Hg vs 123 ± 13.8 mm Hg; P < 0.001), more comorbidities, and lower peak oxygen consumption (19 ± 3 vs 20 ± 4 mL/kg/min; P = 0.021). Patients with HTN had similar NYHA functional class (NYHA functional class II, 72% vs 73%), Valsalva LVOT gradients (72 ± 34 mm Hg vs 74 ± 30 mm Hg), Kansas City Cardiomyopathy Questionnaire–Clinical Summary Scores (70.6 ± 18.8 vs 68.9 ± 23.1), and NT pro–B-type natriuretic peptide levels (geometric mean 632 ± 129 pg/mL vs 745 ± 130 pg/mL). Mavacamten-treated patients had improvement in all primary, secondary, and exploratory endpoints regardless of HTN status or mean SBP. ConclusionsThe clinical benefits of mavacamten in symptomatic, obstructive HCM were similar in patients with and without HTN, despite differences in baseline characteristics. (Clinical Study to Evaluate Mavacamten [MYK-461] in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy [EXPLORER-HCM]; NCT03470545)

Explorations in Non-Binary Poiesis: A Sartorial Path to Wholeness in Queer Body

The path toward coming home to an embodied sense of wholeness in queer identity is often a long journey marked by personal severance. For trans and non-binary people, the arts have become an invaluable space for reclamative wayfinding and liberation. Artistic pathways offer processes to (re)presence the severed parts of ourselves that were laid down to survive in a binary framework that collapses wholeness. Here, I offer forward a sartorial expression of non-binary poiesis as a reclamative act of (re)weaving the lost threads of self. In the disassembling of my adopted aesthetic, sewing and sartorial expressions become a pathway home to wholeness in queer body, where (re)stitching binary endpoints gestures toward a third space for belonging.

Patient-Free Simulation: Analysis of Hospitalized Patients Treated without CT Simulation

Palliative radiation therapy (RT) can be a necessary element of treatment for hospitalized cancer patients who may be critically ill. We have implemented patient-free simulation machine starts using existing diagnostic imaging for treatment planning, eliminating the need for simulation. We hypothesize machine starts reduce time in the department without detriment to clinical outcomes. An IRB-approved database of patients receiving RT was queried for hospitalized patients treated with a machine start. Variables including time on machine and in department, and clinical outcomes were collected. A binary clinical endpoint variable indicated whether the goal of RT was achieved (extubation, hemostasis, etc.). A similar cohort of inpatients receiving CT simulation and mediastinal RT was compared with the machine start group. Mann-Whitney U test was used for comparison between groups. Hypothesis testing for proportions was used to compare patients meeting clinical endpoints. A total of 23 patients were treated with 25 machine starts. The median age was 65 (range 43-82) and median KPS was 50. A total of 15 patients were in the intensive care unit of which 12 were mechanically ventilated (MV). The most common histology was NSCLC (14). RT was most commonly 8-10 Gy in 1 fraction (88%, range 7-30 Gy in 1-10 fractions). Field arrangement was equally weighted AP/PA fields in 84%. Treated sites were mediastinum (17), bone (3), abdomen/pelvis (2), neck (2), and brain (1). Diagnostic CT of the treatment area was obtained a median of 6 days prior to RT (0-57 days). Machine starts within 4 days of admission were significantly more likely to meet the intended clinical endpoint (87% vs 47%, p = 0.02). On day of machine start, patients' median time in the department was 32 minutes (10-141 min). Of machine starts with treatment times available (22), median time in the LINAC vault was 15 minutes (5-31 min). The median shifts from the initial CBCT were 0.9 cm in the superior-inferior direction (0-2.7 cm), left-right 0.9 cm (0-5.9 cm) and anterior-posterior 0.5 cm (0-3 cm). One patient required repeat CBCT after initial shifts. In a similar cohort of patients who underwent CT simulation followed by RT to the mediastinum, the average time in the department was 122 minutes, compared with 45 minutes for machine start patients treated to the mediastinum (p = 0.02). Primary clinical endpoint was achieved in 65% of machine starts. 61% of patients clinically improved and were stable for discharge. Of the MV patients, 42% were successfully extubated and 58% were discharged. Of patients who died (74%), average time to death was 53 days after RT (4-126 days). Among the MV subgroup, 83% died an average of 49 days from RT (4-126 days). Machine starts are a timely and accurate alternative to traditional planning with CT simulation that results in approximately 60% less time in the department. This is an acceptable RT planning technique for a population that demands greater medical attention and resources.

Long-Term Remote vs. Conventional Monitoring of Pacemakers: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Remote monitoring (RM) is the standard of care for patients with cardiac implantable electronic devices (CIEDs), particularly pacemakers. However, the long-term outcomes of RM versus conventional monitoring (CM) of pacemakers and its effectiveness in reducing in-office (IO) visits for device reprogramming require elucidation. This systematic review and meta-analysis aimed to compare the RM and CM of pacemakers over a long-term follow-up. We systematically searched the PubMed/MEDLINE, Embase, Cochrane, and ClinicalTrials.gov databases for randomized controlled trials (RCTs) comparing RM and CM of pacemakers with at least 12 months of follow-up. Binary endpoints were pooled with risk ratios (RRs), whereas continuous outcomes were computed using mean differences (MDs) or standardized MDs (SMDs). Heterogeneity was assessed using I2 statistics. Among the eight included RCTs, 2159 (48.9%) of 4063 patients underwent RM. Follow-up periods ranged from 12 to 24 months. There were no significant between-group differences in all-cause mortality (RR=1.19; 95% confidence interval [CI], 0.90-1.57; p=0.22; I2=0%), stroke (RR=0.90; 95% CI, 0.43-1.91; p=0.79; I2=23%), hospitalizations for cardiovascular and/or device-related adverse events (RR=0.95; 95% CI, 0.75-1.21; p=0.70; I2=0%), and quality of life (SMD=-0.06; 95% CI, -0.22 to 0.10; p=0.473; I2=0%). RM was associated with fewer IO visits/patient/year (MD=0.98; 95% CI, -1.64 to -0.33; p=0.08; I2=98%) and higher rates of atrial tachyarrhythmia (ATA) detection (RR=1.22; 95% CI, 1.01-1.48; p=0.04; I2=0%) than was CM. This meta-analysis suggests that RM of pacemakers leads to higher rates of ATA detection and fewer IO visits/patient/year, without compromising patient safety.

Efficacy and safety of upadacitinib in patients with ankylosing spondylitis refractory to biologic therapy: 1-year results from the open-label extension of a phase III study

BackgroundUpadacitinib, a Janus kinase inhibitor, has demonstrated efficacy and an acceptable safety profile in patients with ankylosing spondylitis (AS) in the phase III SELECT-AXIS programs. We report the 1-year efficacy and safety in patients with AS and an inadequate response to biologic disease-modifying antirheumatic drugs (bDMARD-IR) from the SELECT-AXIS 2 study.MethodsPatients ≥ 18 years with active AS who met the modified New York criteria for AS and were bDMARD-IR received double-blind upadacitinib 15 mg once daily (QD) or placebo for 14 weeks. Patients who completed 14 weeks could enter an open-label extension and receive upadacitinib 15 mg QD for up to 2 years. Efficacy endpoints included the percentage of patients achieving ≥ 40% improvement in Assessment of SpondyloArthritis international Society response (ASAS40), Ankylosing Spondylitis Disease Activity Score (ASDAS) low disease activity (LDA), and ASDAS inactive disease (ID); and change from baseline in total and nocturnal back pain, and Bath Ankylosing Spondylitis Functional Index (BASFI). Subgroup analyses (bDMARD lack of efficacy versus intolerance, and prior tumor necrosis factor inhibitor [TNFi] versus interleukin-17 inhibitor [IL-17i] exposure) were conducted. Binary and continuous efficacy endpoints were assessed using non-responder imputation with multiple imputation (NRI-MI) and as observed (AO) analyses; and mixed-effects model repeated measures (MMRM) and AO, respectively. Safety was assessed based on adverse events. Data through week 52 are reported.ResultsOf 420 randomized patients, 366 (continuous upadacitinib: n = 181; placebo to upadacitinib: n = 185) completed 52 weeks of treatment. At week 52, in the continuous upadacitinib and placebo to upadacitinib groups, ASAS40, ASDAS LDA, and ASDAS ID were achieved by 66% and 65%, 57% and 55%, and 26% and 25% (all NRI-MI); and change from baseline in total back pain, nocturnal back pain, and BASFI was -4.5 and -4.3, -4.6 and -4.4, and -3.6 and -3.5 (all MMRM), respectively. No new safety risks were identified. Subgroup analyses were consistent with the overall study population.ConclusionsUpadacitinib 15 mg QD demonstrated sustained improvement up to 52 weeks in bDMARD-IR patients with AS. Efficacy was generally similar in patients with lack of efficacy versus intolerance to bDMARDs and prior TNFi versus IL-17i exposure.Trial registrationNCT02049138.

Bayesian estimation of the binomial parameter in sequential experiments.

This article presents an objective Bayesian approach to estimating the binomial parameter in group sequential experiments with a binary endpoint. The idea of deriving design-dependent priors was first introduced using Jeffreys criterion. Another class of priors was developed based on the reference prior theory. A theoretical framework was established showing that explicit reference to the experimental design in the prior is fully Bayesian justified. Using a design-dependent prior which generalizes the reference prior, I propose a comprehensive and unified approach to the point and the interval estimations in group sequential experiments, and I evidence the good frequentist properties of the posterior estimators through comparative studies with the existing methods. The effect of the prior correction on the posterior estimates is studied in three classical designs of clinical trials. Finally, I discuss the idea of using this approach as a default choice for estimation upon sequential experiment termination.

Surgical versus non-surgical treatment of flail chest: a meta-analysis of randomized controlled trials.

Conflicting evidence exists on the choice of surgical or non-surgical treatment of flail chest injuries. We aimed to perform a meta-analysis comparing outcomes in patients presenting flail chest undergoing surgical or non-surgical treatment. Embase, PubMed, and Cochrane databases were searched for randomized controlled trials (RCTs) comparing surgery to no surgery in patients with acute unstable chest wall injuries. We computed weighted mean differences (WMDs) for continuous outcomes and risk ratios (RRs) for binary endpoints, with 95% confidence intervals (CIs). Random effects meta-analyses were performed. Heterogeneity was assessed using I2 statistics. Six RCTs (544 patients) were included, and surgical treatment was used in 269 (49.4%). Compared to no surgery, surgery reduced mechanical ventilation days (WMD -4.34, 95% CI -6.98, -1.69; p < 0.01; I2 = 87%; GRADE: very low; PI -13.51, 4.84); length of intensive care unit stay (WMD -4.62, 95% CI -7.19, -2.05; p < 0.01; I2 = 78%; GRADE: low; PI -12.86, 3.61) and the incidence of pneumonia (RR 0.50, 95% CI 0.31, 0.81; p = 0.005; I2 = 54%; GRADE: moderate; PI 0.13, 1.91). No difference in mortality (RR 0.56, 95% CI 0.19, 1.65; p = 0.27; I2 = 23%; GRADE: moderate; PI 0.04, 7.25), length of hospital stay (WMD -5.39, 95% CI -11.38, -0.60; p = 0.08; I2 = 89%; GRADE: very low; PI -11.38, 0.60), or need for tracheostomy (RR 0.59, 95% CI 0.34, 1.03; p = 0.06; I2 = 54%; GRADE: moderate; PI 0.11, 3.24) was found. Our results suggest that surgical treatment is advantageous compared to non-surgical treatment for patients with flail chest secondary to rib fractures.

Poster 212: Return to Sport Rate of Collegiate Athletes Following Primary Hip Arthroscopy for Femoroacetabular Impingement

Objectives: Athletic participation has been increasingly associated with symptomatic femoroacetabular impingement (FAI). High-intensity and repetitive sporting activities, especially those involving “at-risk” hip positions, can increase the risk for developing FAI. Numerous studies have shown that elite athletes can return to play at the professional level after undergoing hip arthroscopy. However, there is minimal data on return to sport rate and outcomes at the collegiate level. The purpose of this study is to determine the return to sport (RTS) rate of collegiate athletes following hip arthroscopy for treatment of FAI. Methods: Patients who were collegiate athletes and underwent hip arthroscopy surgery for treatment of FAI performed by a single surgeon between January 2010 and May 2020 were included. Patients who were in their final year of eligibility, graduated, retired or had plans to retire from collegiate play prior to surgery, or who had undergone prior ipsilateral hip surgery were excluded. Publicly available data was collected on each patient’s collegiate team and division, RTS status after surgery, and level of play after surgery. Successful RTS was defined as competing in a competition at the collegiate level after surgery. If both hips were operated on during the same season, then RTS was the same for both hips. Comparisons between RTS and no RTS groups were performed with the Mann-Whitney U test for continuous endpoints and Fisher’s exact test or Pearson’s Chi-squared test for categorical or binary endpoints. Results: A total of 181 hips (in 148 unique athletes) met inclusion criteria comprised of 114 male (63%) and 67 female (37%) hips with mean age of 20.5±1.5 (Table 1). Thirty-eight patients had bilateral hip arthroscopy. Patients were collegiate athletes in 19 different sports with football (17% of hips), soccer (15%), ice hockey (14%), and baseball (8%) the most commonly played (Table 2). The majority of patients played at the Division I level (n=140 hips, 79%). There were 19 patients with borderline dysplasia (lateral center-edge angle (LCEA)=20-25 degrees) and 7 patients with dysplastic hips (LCEA &lt;20 degress). Severe cartilage defects (Outbridge III/IV) were found in 41 hips (23%) with 15 hips (8%) undergoing microfracture. Eighty-six percent (155 hips) returned to sport at the collegiate level following hip arthroscopy. Males were significantly less likely to RTS compared to females (82% vs 93%, OR = 2.8, 95% CI [1.003, 7.819], p=0.042). Patients who RTS did have a marginally statistically significantly higher mean pre-operative SF-12 MCS compared to those who did not (55±9 vs 51±9, p=0.050). There was no signficiant association between the RTS and no RTS groups with respect to preoperative alpha angle, minimum joint space, LCEA or dysplasia category, collegiate division, presence or treatment of severe cartilage defect, or pre-operative outcome scores relating primarily to pain or physical function (mHHS, HOS-ADL, HOS-Sport, SF-12 PCS) (p&gt;0.05 for all). Conclusions: There is a high return to sport rate among collegiate athletes following hip arthroscopy for the treatment of FAI. Male athletes and those with lower preoperative SF-12 MCS scores may be at risk for lower likelihood of return to collegiate competition. [Table: see text][Table: see text]