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Introduction Linvoseltamab is an investigational, BCMA×CD3 bispecific antibody designed for the treatment of RRMM. High objective response rates (ORR) to linvoseltamab 200 mg in the LINKER-MM1 trial (NCT03761108) were demonstrated across high-risk subgroups, including patients aged ≥75 years, patients with high-risk cytogenetics, and patients with penta-class refractory status. The aim of this study was to compare ORR, overall and in key subgroups, between patients in Phase 2 of the LINKER-MM1 trial and patients in an international RW SOC external control arm (ECA). Methods The ECA was derived from a chart review of 16 academic sites across 10 countries that are part of the International Myeloma Foundation (IMF)-International Myeloma Working Group (IMWG) and 2 US electronic health record databases (COTA and Guardian Research Network [GRN]). Included patients initiated ≥1 anti-MM treatment after meeting key eligibility criteria of LINKER-MM1. Weighted random sampling and inverse probability of treatment weighting (IPTW) were used to select 1 line of therapy (LOT) per patient and balance the overall ECA and trial populations on prespecified prognostic factors (Kumar S, et al. IMS 2023). For ORR assessment, LINKER-MM1 and IMF-IMWG used independent central review committees per IMWG criteria, COTA used algorithmic assessment based on IMWG criteria, and GRN used physician-assessed responses. Prior to conducting comparative analyses, an independent committee of epidemiology and oncology experts reviewed the comparability of the cohorts and endpoint assessments, and approved study continuation. ORR among patients in LINKER-MM1 and patients in the ECA was compared overall and across prespecified subgroups (≥10 patients per subgroup), including age, race, cytogenetic risk score, international Staging System (ISS), presence of extramedullary plasmacytoma (EMP), refractory class, bone marrow plasma cell (BMPC) proportion, and number of prior LOTs. Results Median duration of follow-up was 14.3 months (data cut-off: January 6, 2024) for patients receiving linvoseltamab (n=105) and 13.6 months for the ECA (n=307; n=194, n=72, and n=41 from IMF-IMWG, COTA, and GRN, respectively). Following IPTW, 13 prognostic factors with <30% missingness were balanced between cohorts, with an effective sample size in the ECA of 197. After adjustment, ORR was significantly higher in patients who received linvoseltamab compared with patients in the ECA (69.5% vs 45.7%, odds ratio [OR] 2.5 [95% confidence interval (CI) 1.6-4.1]) and in key subgroups with age 65-74 years (76.9% vs 48.3%, OR 3.6 [1.6-8.6]), age ≥75 years (72.4% vs 48.5%, OR 2.8 [1.1-7.4]), Black or African American race (82.4% vs 25.0%, OR 14.0 [3.0-85.4]), White race (68.9% vs 49.7%, OR 2.2 [1.3-4.0]), standard cytogenetic risk (72.3% vs 51.3%, OR 2.5 [1.3-4.8]), ISS stage III (58.8% vs 19.7%, OR 5.8 [1.5-25.2]), absence of EMP (71.6% vs 49.3%, OR 2.6 [1.5-4.6]), triple-class refractory status (68.2% vs 45.7%, OR 2.6 [1.5-4.4]), quadruple-class refractory status (66.7% vs 45.9%, OR 2.4 [1.3-4.3]), 4-5 prior LOTs (65.1% vs 40.4%, OR 2.8 [1.3-6.0]), and >5 prior LOTs (75.7% vs 36.1%, OR 5.5 [2.4-13.6]). Numerically higher (not statistically significant) or similar ORR was observed for patients receiving linvoseltamab compared with patients in the ECA with age <65 years (59.5% vs 46.8%, OR 1.7 [0.79-3.6]), high-risk cytogenetics (65.0% vs 63.1%, OR 1.1 [0.41-2.9]), ISS stage I (73.3% vs 64.6%, OR 1.5 [0.62-3.7]), ISS stage II (67.6% vs 53.5%, OR 1.8 [0.72-4.7]), presence of EMP (58.8% vs 56.9%, OR 1.1 [0.32-3.8]), penta-class refractory status (64.3% vs 48.5%, OR 1.9 [0.78-4.8]), BMPC <50% (77.0% vs 67.2%, OR 1.6 [0.61-4.3]), BMPC ≥50% (41.7% vs 36.0%, OR 1.3 [0.36-4.7]), and ≤3 prior LOTs (68.0% vs 66.4%, OR 1.1 [0.43-2.9]). Separate findings will be presented for IMF-IMWG and COTA/GRN data at the congress. Conclusions Linvoseltamab induced better ORR vs RW SOC treatments overall, and better or similar ORR in the key subgroups assessed, highlighting its therapeutic value across a range of patients with RRMM with heterogeneous risk profiles and levels of disease burden.

Objective The 2019 European Alliance of Associations for Rheumatology (EULAR)/American College of Rheumatology (ACR) systemic lupus erythematosus (SLE) classification criteria score (≥20 points) has been associated with poor outcomes. We aimed to evaluate its utility as a predictor for mortality and hospitalisation and to derive and validate an ominosity score based on the SLE classification criteria set. Methods Incident patients with SLE in a population-based cohort were included. The association between the 2019 EULAR/ACR SLE score and mortality and hospitalisation was assessed using Cox regression adjusted for age, sex and calendar year. An ominosity score for mortality was developed based on the SLE criteria set. The least absolute shrinkage and selection operator method was used to estimate model coefficients. Concordance and calibration were assessed by cross-validation and by plotting the observed event rates against the deciles of predicted probabilities. Results Among 374 patients with incident SLE, a EULAR/ACR score ≥20 points was not associated with an increased risk of mortality (HR 1.17, 95% CI 0.67 to 2.03) or first hospitalisation (HR 1.14, 95% CI 0.79 to 1.64) compared with a score ≤19 points. The derived ominosity score for mortality included age, sex, thrombocytopaenia, neuropsychiatric manifestations, subacute cutaneous or discoid lupus, non-scarring alopecia, inflammatory arthritis, renal involvement, antiphospholipid antibodies and hypocomplementaemia. This model demonstrated a concordance=0.76 with adequate calibration. Age and sex were the main predictors, as seen in the model including just age, sex and year (concordance=0.77). Conclusion The 2019 EULAR/ACR SLE criteria score was not associated with mortality and hospitalisation. The derived ominosity score for mortality presented good prediction for mortality but was not better than age and sex alone.

Abstract Objective To assess the association of aPL and diffuse alveolar haemorrhage (DAH) in patients with SLE by performing a systematic review and meta-analysis. Methods Multiple databases were systematically searched from inception to February 2024. Studies were eligible if they included patients with SLE (population), reported aPL status (exposure), and DAH (outcome). We pooled the estimates as odds ratio (OR) using fixed-effect models. We examined the association between aPL and DAH, as well as associations based on aPL subtypes or concomitant APS. Results Out of 454 screened studies, nine were included in meta-analysis, encompassing 7746 patients with SLE, of whom 2016 (26.0%) were aPL-positive and 163 (2.1%) had DAH. Patients with SLE and positive aPL (any) were more likely to develop DAH than aPL-negative patients (OR = 1.76, 95% CI 1.24–2.49; I2 = 0%). Patients with SLE and positive LA (OR = 1.76, 95% CI 1.06–2.93, I2 = 35%) or positive anticardiolipin IgG (OR = 1.62, 95% CI 1.13–2.34, I2 = 0%) had a higher likelihood of developing DAH compared with patients that were negative for these aPL. An APS diagnosis was associated with a 2.5-fold increased likelihood of DAH compared with subjects without APS (OR = 2.46, 95% CI 1.23–4.92, I2 = 0%). Positivity of anti-β2 glycoprotein I IgG was not significantly associated with DAH among patients with SLE (OR = 0.78, 95% CI 0.45–1.36, I2 = 0%). Conclusion In patients with SLE, aPL positivity increases the risk of DAH compared with aPL-negative patients, particularly in those positive for LA and anticardiolipin IgG.

BACKGROUND: In severely symptomatic patients with obstructive hypertrophic cardiomyopathy (HCM), VALOR-HCM trial (Study to Evaluate Mavacamten in Adults With Symptomatic Obstructive HCM Who Are Eligible for Septal Reduction Therapy [URL: https://clinicaltrials.gov ; Unique identifier: NCT04349072]) reported that mavacamten reduced the short-term need for septal reduction therapy (SRT). The current report examined the longer-term effect of mavacamten through end of treatment at week 128. METHODS: A double-blind randomized placebo-controlled multicenter trial at 19 sites in the United States included symptomatic obstructive HCM patients referred for SRT (enrollment July 2020 through October 2021). The group initially randomized to mavacamten continued the drug for 128 weeks and the placebo to mavacamten group from week 16 to 128 (112-week exposure). Dose titrations were performed using echocardiographic left ventricular outflow tract gradient and left ventricular ejection fraction measurements. The principal end point was proportion of patients proceeding with SRT or remaining guideline-eligible at week 128. RESULTS: At week 128, 17 of 108 (15.7%) patients in the total study sample met the composite end point (7 underwent SRT, 1 was SRT-eligible, and 9 SRT-status unevaluable). Additionally, 87 of 108 (80.5%) patients demonstrated ≥1 New York Heart Association class improvement by week 128, and 52 of 108 (48.1%) demonstrated ≥2, with a sustained reduction in resting and Valsalva left ventricular outflow tract gradients of 38.2 mm Hg and 59.4 mm Hg, respectively. Ninety-five of 108 (88%) patients transitioned to commercial mavacamten. Overall, 15 of 108 (13.8%) patients (5.41 per 100 patient-years) had an left ventricular ejection fraction <50% (2 with left ventricular ejection fraction ≤30%; 1 death). Of these, 12 of 15 (80%) continued treatment. New-onset atrial fibrillation occurred in 11 (10.2%) patients (4.55 per 100 patient-years). CONCLUSIONS: In severely symptomatic obstructive HCM patients, sustained freedom from SRT was observed at 128 weeks, with nearly 90% patients remaining on long-term mavacamten. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04349072.

A BSTRACT Purpose/Background: To identify the proportion of patients with prediabetes who have prescribed metformin and factors related to doing so as a preventive measure for diabetes in primary care at a Family Medicine Unit in northeastern Mexico. Methods: This retrospective observational study included 372 adults who met the criteria for prediabetes diagnosis according to the American Diabetes Association. Data was collected from medical records from January 2020 to December 2021. Possible associations between the variables of interest and the prescription of metformin were tested via hypothesis tests, furthermore, binary logistic regression was performed. Results: Nearly 85% of the patients met at least one criterion for receiving metformin according to ADA recommendations, but only 60% of them were prescribed this medication. Patients with metformin prescriptions differed from those without in aspects such as having a documented diagnosis of prediabetes in their medical records, a higher BMI, and higher glucose levels. Conclusions: Almost one out of two patients with a high risk of type 2 diabetes are not treated with metformin as a preventive measure. Factors associated with metformin prescription included a high BMI, elevated baseline glucose levels, and a prediabetes diagnosis in the medical record. These findings suggest the need for studies to evaluate physicians’ reasons for different treatments and implementation of recommendations for type 2 diabetes prevention in patients with prediabetes in primary health care.

Purpose: Autologous serum tears (ASTs) are produced from serum obtained by blood draw and used to treat severe dry eye diseases. Multiple cases of failed AST production occurred due to serum becoming a solidified, gel-like substance after centrifugation. The aim of this study was to identify risk factors associated with inability to compound AST. Methods: From January 2019 to December 2022, 99 patients received AST produced at Mayo Clinic in Arizona. Patient demographics, medical diagnoses, medications, laboratory results, and events surrounding blood draws were obtained through an IRB-approved retrospective chart review. The laboratory and pharmacy protocol procedures were observed in person after the occurrence of the last production issue. Results: Ten total clotted serum episodes occurred in 4 patients, each with multiple occurrences. The indication for AST was chronic ocular graft-vs-host disease (n = 3) and Sjögren syndrome (n = 1). Eighty percent of episodes were associated with either a systemic infection (n = 7) or pulmonary embolism (n = 1) within the prior month. At the time of blood draw, all 4 patients were treated with antiplatelet and/or anticoagulation medications, including rivaroxaban, apixaban, aspirin, and low–molecular-weight heparin. Conclusions: The AST protocol was increased from 30 to 60 minutes of resting time to allow clotting before centrifugation. Inadequate clotting during this stasis period likely resulted in fibrinogen remaining suspended in the serum, leading to solidified plasma instead of liquid serum. We hypothesize risk of inadequate clotting would be increased in patients taking anticoagulation or antiplatelet medications. Our recommendations include ensuring 60-minute collection tube resting time for all patients, including those on anticoagulation medication.

Background: Penile inversion vaginoplasty (PIV) entails considerable soft-tissue dissection to the perineal region and involves complex tissue rearrangement. This study examines the role of an enhanced recovery after surgery (ERAS) pathway after PIV in reducing opioid use and controlling postoperative pain. Methods: A retrospective study of 50 transfemale patients who underwent PIV at a single institution from June 2021 to January 2023 was completed. The study compared 2 groups of patients who were given different postoperative pain management regimens: group A received standard postoperative analgesics and group B received ERAS. Variables such as postoperative pain scores on the numeric pain rating scale (0–10), use of opioid medication, length of hospital stay, and patient comorbidities were recorded and compared across the 2 groups. Results: The average hospital stay length was 4.92 (±0.85) days. Group A had a slightly longer average stay compared with group B. The average pain level in both groups was 4.25 (SD ±1.51). Group A exhibited a slightly higher average pain level of 4.31 (±1.53), whereas group B exhibited 4.16 (SD±1.51) (P = 0.77). Although pain levels did not significantly vary between the 2 groups, there was a statistically significant decrease in the amount of opioid medication used in group B with a P value of 0.009. Conclusions: ERAS protocol is effective in decreasing opioid usage in the immediate postoperative setting after PIV.

Abstract Purpose: The three-arm, phase III KEYNOTE-361 study did not meet its dual primary endpoints of progression-free survival (PFS) or overall survival (OS) with first-line pembrolizumab plus chemotherapy versus chemotherapy in advanced urothelial carcinoma. This prespecified exploratory analysis assessed the association of tumor mutational burden (TMB) and PD-L1 combined positive score (CPS) with clinical outcomes. Patients and Methods: TMB and PD-L1 CPS were determined via whole-exome sequencing and PD-L1 IHC 22C3 pharmDx, respectively. The association was evaluated in each treatment arm using logistic regression [objective response rate (ORR)] and Cox proportional hazards regression models (PFS and OS); one-sided (pembrolizumab monotherapy; pembrolizumab plus chemotherapy) and two-sided (chemotherapy) nominal P values were calculated. Significance was prespecified at α = 0.05 without multiplicity adjustment. Efficacy was evaluated by prespecified cutoffs of 175 mutations/exome (TMB) and CPS 10 (PD-L1). Results: Of the 993 treated patients, 820 (82.6%) and 993 (100%) had evaluable TMB and CPS data, respectively. Continuous TMB was positively associated with ORR, PFS, and OS for pembrolizumab monotherapy (one-sided P &lt; 0.001, P &lt; 0.001, and P = 0.007, respectively); PFS and OS for pembrolizumab plus chemotherapy (one-sided P = 0.007 and P = 0.010, respectively); and OS for chemotherapy alone (two-sided P = 0.040). Continuous PD-L1 CPS showed evidence of anticipated association with ORR and PFS for pembrolizumab monotherapy. The subgroup with TMB ≥175 mutations/exome and PD-L1 CPS ≥10 had the highest PFS and OS improvements with pembrolizumab alone or with chemotherapy versus chemotherapy alone. Conclusions: These data suggest that TMB may be predictive of the response to pembrolizumab alone or with chemotherapy in advanced urothelial carcinoma.