ProHealth Care

Objective: The objective of this open-label, interventional, prospective clinical study was to evaluate the effectiveness of a multimodal wound matrix (MWM) in moving chronic, nonhealing wounds that had failed prior therapies onto a healing trajectory. The overall response rate was the proportion of subjects who had greater than 40% reduction in size after 4 weeks of treatment. Secondary objectives included the percentage area reduction (PAR) after 4 and 12 weeks, incidence of ulcer closing, and changes in quality of life. Approach: An open-label, interventional, prospective cohort, real-world evidence study was conducted following the STROBE criteria. Criteria included chronic nonhealing wounds of multiple etiologies in subjects with extensive comorbidities. Results were compared with data from the U.S. Wound Registry. Results: A total of 111 subjects entered the screening phase and 64 were treated. Fifty-three wounds were eligible for the dataset that included 18 diabetic foot ulcers, 19 venous leg ulcers, 2 pressure injuries, 1 surgical, 1 lower extremity wound, and 12 unclassified etiologies. The objective response rate was 42%. The 4-week PAR was 34%. The 12-week PAR was 66%. Eighteen wounds closed by week 12. Innovation: MWM is a formulation technology developed to address the major obstacles that prevent healing. Results were evaluated in a patient population with extensive comorbidities that had failed prior treatments and would be generally excluded from controlled trials. Conclusion: The results from this study support the contention that MWM achieves substantial clinical improvement in a complex patient population not enrolled in clinical trials and demonstrates an advancement in wound management.

Immune checkpoint inhibitors (ICIs) targeting programmed cell death protein 1 (PD-1), programmed cell death ligand 1 (PD-L1), and cytotoxic lymphocyte-associated antigen-4 (CTLA-4) have revolutionized cancer treatment but are associated with immune-related adverse events, particularly cutaneous toxicities. We report a rare case of pembrolizumab-exacerbated pigmented purpuric dermatosis (PPD) in a 77-year-old male with a history of metastatic non-small cell lung cancer. His rash, initially confined to the lower extremities, worsened and became widespread to involve the trunk after pembrolizumab initiation. Histopathology showed perivascular lymphocytic infiltrate with extravasated erythrocytes without vasculitis, compatible with PPD; however, due to some lymphocyte atypia and exocytosis, together with the clinically widespread lesions, there was initial concern for PPD-like mycosis fungoides (MF). Subsequent T-cell receptor gene rearrangement studies revealed no monoclonal lymphoid population, and the later resolution of the rash with treatments typical for PPD did not support MF. This represents only the second reported case of ICI-associated PPD and highlights a potential diagnostic pitfall with histopathology and clinical presentation mimicking PPD-like MF. Our case contributes to the expanding spectrum of ICI-related cutaneous reactions and underscores the importance of recognizing inflammatory dermatoses with atypical histopathologic features for dermatologists and dermatopathologists.

INTRODUCTION: Prior studies show differences in posterior compartment structures on magnetic resonance imaging (MRI) between resting and straining in patients with pelvic organ prolapse when compared to age- and parity-matched controls (Lewicky-Gaupp 2010). Further, nulliparous older women (>70) have larger resting levator bowl volume than younger women (<40) (Swenson 2020). OBJECTIVE: In this MRI measurement technique development pilot study, we perform a detailed analysis of the posterior compartment structures at rest and with straining in young, nulliparous subjects without prolapse symptoms and compare these MRI measurements to their POP-Q measurements. METHODS: Six OBGYN physicians from differing institutions and career stages met weekly to learn pelvic floor MRI measurement techniques. Using an MRI biorepository, mid-sagittal images were analyzed at rest and with straining in nulliparous subjects aged <40 years without prolapse symptoms. We utilized 3D Slicer software (slicer.org) to measure posterior vaginal wall length (PVW), urogenital hiatus (UGH), levator hiatus (LH), levator plate length (LP), and levator bowl volume (LBV). Six independent evaluators, five of which were novices, performed measurements that were averaged, and interrater reliability was assessed using the intraclass correlation coefficient (ICC). Statistical analysis was performed using Python; independent t-test and Pearson correlation were utilized. RESULTS: Eleven subjects were available for analysis. Table 1 shows demographic characteristics. Compared with resting measurements, UGH (p<.001), LH (p<.001), and LBV (p<.001) increased with straining without significant change in LP or PVW length. There was a strong positive correlation between MRI posterior fornix location and PVW length (r=.77, p<.001). There was a strong negative correlation between MRI cervix location and POP-Q C (r= −0.70, p=.01) and MRI posterior fornix and POP-Q D (r=−0.697, p=.02). ICC was .95 indicating excellent interrater reliability (Figure 1). CONCLUSIONS: MRI allows visualization of real-time changes within the same subject and provides insight into the biomechanics of the pelvic floor beyond what can be learned from textbooks and cadaveric dissections. In young, nulliparous women without prolapse symptoms, MRI reveals dynamic changes in posterior compartment structures between rest and strain. During straining, there is relaxation of the pelvic floor shown by increased UGH, LH, and LBV. Although straining did not change the length of LP or PWV, it likely changed the orientation of the levator plate, as evidenced by the increase in LBV. The strong correlations between MRI measurement and POP-Q measures reflect that these measures describe the same phenomenon. The ICC for this study showed excellent interrater reliability, demonstrating that targeted education and training in pelvic MRI analysis produces precise and accurate measurement results among novice learners (Table 2).

Despite randomized data for survival benefit (with class 1 recommendations) for treating heart failure (HF) with reduced ejection fraction using quadruple medical therapy (QMT)-defined as evidence-based β-blockers, sodium-glucose cotransporter 2 inhibitor, preferably angiotensin receptor/neprilysin inhibitor, and mineralocorticoid receptor antagonist-it is underutilized. IMPLEMENT-HF is a multiregional HF quality improvement initiative to improve care and outcomes for patients with HF by enhancing the use of QMT in routine practice. This analysis of HF with reduced ejection fraction treatment in patients from hospitals participating in the American Heart Association's Get With The Guidelines-HF who volunteered to participate in IMPLEMENT-HF in 7 US regions. IMPLEMENT-HF included multidisciplinary learning to share strategies for formulary changes, electronic health record tools, and patient resources with site-level feedback reports. Participants gathered QMT data at discharge and 30 days after discharge. We evaluated QMT utilization and variation, in addition to other prespecified performance measures, from Q1 2021 to Q2 2023. The median (interquartile range) age of 43 558 admitted patients at 61 hospitals was 74 (63-83) years; 16 530 (38%) belonged to racial and ethnic minorities, and 22 228 (51%) were women. Between Q1 2021 and Q2 2023, defect-free QMT improved from 4.7% to 44.6% at discharge and from 0% to 44.8% at 30 days (both P<0.0001). There was also substantially improved incorporation of health-related social needs assessments. The magnitude of improvements was similar when stratified by sex or race and ethnicity, yet there was significant regional variation. Among healthcare systems participating in IMPLEMENT-HF, there was a marked increase in QMT use among eligible patients over the course of the initiative. This quality improvement initiative supports a learning collaborative model to promote improvements in QMT use.

BackgroundPatients with advanced/recurrent endometrial cancer have a poor prognosis and limited treatment options. Biomarkers such as tumor protein 53 (TP53) in endometrial cancer can integrate novel strategies for improved and individualized treatment that could impact patient outcomes. In an exploratory analysis of the phase III ENGOT-EN5/GOG-3055/SIENDO study of selinexor maintenance monotherapy 80 mg in advanced/recurrent endometrial cancer, a pre-specified subgroup of patients with TP53 wild type (wt) endometrial cancer showed preliminary activity at long-term follow-up with a generally manageable safety profile (median progression-free survival 27.4 months vs 5.2 months placebo, HR=0.41).Primary ObjectiveTo evaluate the efficacy of selinexor compared with placebo as maintenance therapy in patients with advanced or recurrent TP53wt endometrial cancer.Study HypothesisSelinexor administered at 60 mg weekly as maintenance therapy will show manageable safety and maintain efficacy in patients with TP53wt advanced/recurrent endometrial cancer after systemic therapy versus placebo.Trial DesignThis is a prospective, multicenter, double-blind, placebo-controlled, randomized phase III study designed to evaluate the efficacy and safety of selinexor as a maintenance therapy in patients with advanced or recurrent TP53wt endometrial cancer.Major Inclusion/Exclusion CriteriaEligible patients must have histologically confirmed endometrial cancer, TP53wt confirmed by next-generation sequencing, completed at least 12 weeks of platinum-based therapy with or without immunotherapy, with confirmed partial response or complete response, and primary Stage IV disease or at first relapse.Primary EndpointThe primary endpoint is investigator-assessed progression-free survival per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 in the intent-to-treat population.Sample SizeA total of 220 patients will be enrolled.Estimated Dates for Completing Accrual and Presenting ResultsAccrual is expected to be completed in 2024 with presentation of results in 2025.Trial RegistrationNCT05611931

TPS7094 Background: FL and MZL are indolent B-cell non-Hodgkin lymphomas (B-NHLs) that are treated in a similar way in the R/R setting. Despite the efficacy of rituximab–lenalidomide (R2) in patients (pts) with R/R FL, and MZL to a lesser extent, a notable proportion fail to achieve an optimal, durable response. Odronextamab is an off-the-shelf, CD20×CD3 bispecific antibody. In the Phase (Ph) 1 ELM-1 study, odronextamab monotherapy showed antitumor activity and a generally manageable safety profile across R/R B-NHL subtypes, including FL and MZL (Bannerji, et al. Lancet Haematol 2022). In the Ph 2 ELM-2 study, odronextamab elicited an objective response rate of 80% and complete response (CR) rate of 73% in pts with heavily pretreated R/R FL (Villasboas, et al. ASH 2023). The rate of treatment-related adverse events leading to treatment discontinuation was 7.8%. These positive data support the evaluation of odronextamab in R/R FL and MZL in earlier lines of therapy. Combining odronextamab with lenalidomide has the potential to improve efficacy in the R/R setting compared with R2. Methods: OLYMPIA-5 (NCT06149286) is a Ph 3, open-label, randomized study of odronextamab plus lenalidomide versus R2 in pts with R/R FL and MZL. The study consists of Part 1 (safety run-in) followed by Part 2 (randomization). In Part 1, odronextamab and lenalidomide will be administered for 12×28-day cycles or until relapse, progressive disease, withdrawal of consent, or unacceptable toxicity. Odronextamab IV infusion will be administered in a step-up regimen during Cycle (C) 1 to mitigate the risk of cytokine release syndrome, followed by full dose starting from C1 Day 22. In Part 2, pts will be randomized 1:1 to receive 12 cycles of odronextamab plus lenalidomide, or R2 for the first 5 cycles followed by lenalidomide monotherapy for C6–12 per standard schedule (Leonard, et al. J Clin Oncol 2019). Key inclusion criteria: aged ≥18 years; histologically confirmed FL Grade 1–3a or MZL (nodal, splenic, or extra nodal) that is refractory or relapsed after ≥2 cycles of prior systemic therapy that included ≥1 anti-CD20 antibody; measurable disease; ECOG PS 0–2; and adequate organ function. Pts with central nervous system (CNS) lymphoma, history of or current relevant CNS pathology, histological evidence of transformation to high-grade or diffuse large B-cell lymphoma, and prior use of lenalidomide or any CD20×CD3 bispecific antibody within the past 6 months are excluded. The Part 2 primary endpoint is progression-free survival as assessed by independent central review. Key secondary endpoints are CR, best overall response, and overall survival. Minimal residual disease (by ctDNA) analysis is an exploratory endpoint. The trial is currently recruiting and is expected to enroll approximately 24–48 pts in Part 1 and 422 pts in Part 2 (352 R/R FL; 70 R/R MZL) at ~200 global sites. Clinical trial information: NCT06149286 .

Introduction/BackgroundIn the phase 3 RUBY trial (NCT03981796) of patients with primary advanced or recurrent endometrial cancer (pA/rEC), dostarlimab+carboplatin-paclitaxel significantly improved progression-free survival (PFS) versus carboplatin-paclitaxel alone in the mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) and overall populations with a statistically significant and clinically meaningful benefit in the overall population. Here we report on PFS2-PFS1 (defined as time from disease progression to the date of progression on the first subsequent anticancer therapy following study treatment or death by any cause) in the RUBY trial.Methodology>Patients with pA/rEC were randomised 1:1 to dostarlimab+carboplatin-paclitaxel or placebo+carboplatin-paclitaxel Q3W (6 cycles) followed by dostarlimab or placebo monotherapy Q6W ≤3 years or disease progression. PFS2-PFS1 was a post hoc analysis in all populations.ResultsOf 494 patients randomized (245 dostarlimab+carboplatin-paclitaxel; 249 placebo+carboplatin-paclitaxel), 118 were dMMR/MSI-H (53 dostarlimab+carboplatin-paclitaxel; 65 placebo+carboplatin-paclitaxel). In the dMMR/MSI-H population, median PFS2-PFS1 was longer in the dostarlimab+carboplatin-paclitaxel arm (17.7 vs 10.5 months; HR, 0.77; figure 1). In the mismatch repair proficient/microsatellite stable (MMRp/MSS) population, median PFS2-PFS1 was numerically higher (7.9 vs 7.1 months; HR, 0.82) favouring dostarlimab+carboplatin-paclitaxel; notably, the survival curves progressively separate after approximately 3 months and remain separated. Median PFS2-PFS1 in the overall population was also numerically higher with dostarlimab+carboplatin-paclitaxel (7.9 vs 7.3 months; HR, 0.82). 462 Figure 1ConclusionIn the RUBY trial of patients with pA/rEC, longer PFS2-PFS1 in the dMMR/MSI-H population suggests that patients continue to derive benefit from dostarlimab treatment following disease progression. In the MMRp/MSS population, the early and progressive separation of the KM curves suggest that the PFS1 benefit of immunotherapy+carboplatin-paclitaxel may translate into better long-term outcomes, including PFS2 and eventually overall survival. Overall, these results suggest that the sequencing of dostarlimab+carboplatin-paclitaxel as 1L treatment provides benefit beyond PFS1 into PFS2. This provides further support for dostarlimab+carboplatin-paclitaxel as standard-of-care in pA/rEC.DisclosuresThis study (NCT03981796) was sponsored by GSK, Waltham, MA, USA.Third-party medical writing support: Writing and editorial support, funded and coordinated by GSK (Waltham, MA, USA), was provided by Shannon Morgan-Pelosi, PhD, and Jennifer Robertson, PhD, of Ashfield MedComms, an Inizio company.COI: Dr McCourt reports personal royalties <$200 annually from UpToDate; and personal honoraria of $200 from the Washington University OB/Gyn annual symposium.Dr Shahin reports institutional grants from AstraZeneca, GSK, and Merck; honoraria from AstraZeneca, GSK, Merck, and Seagen; expert testimony fees from Robindon & Havens PSC, Lexington KY; advisory board fees from Seagen; and board member for Unite for Her.Dr Kristeleit reports Grants from Clovis and MSD; honoraria and consultancy fees from Basilea Pharmaceutica, MSD, AstraZeneca, Clovis, Eisai, Incyte, and Pharmamar; and personal fees from GSK.Dr Willmott reports speakers’ bureau fees from Astra Zeneca, Eisai, Immunogen, Merck, and Seagen, and advisory board fees from AstraZeneca, Immunogen, and Seagen.Dr Barlin reports participation on the FLORA and XPORT steering committees, participation in advisory boards for AstraZeneca, Clovis, Mersana, OncoC4, and Immunogen, and participation in speaker’s bureaus for AstraZeneca and Merck.Dr Gilbert reports institutional grants from Alkermes, AstraZeneca, Clovis, Esperas, ImmunoGen Inc, IMV, Karyopharm, Merck Sharp & Dohme, Mersana, Novocure GmbH, OncoQuest Pharmaceuticals, Pfizer, Roche, and Tesaro; consulting fees from Merck; and honoraria from Alkermes, AstraZeneca, Eisai, Eisai-Merck, and GSK.Dr Cloven reports participation in advisory boards for GSK, Kartos, Novita, Takeda, Toray, Umoja, and Zentalis.Dr Bjørge reports grants/research support from AstraZeneca, honoraria/consulting fees from Onsanger, and participation in a company-sponsored speakers’ bureau for MSD.Dr Black reports institutional grant fees from GSK; fees for being a member of GOG Partners Investigational Council; and medical director/owner of Trials365, LLC.Dr Mathews reports institutional research funding from AvengeBio Astellas Pharma, AstraZeneca, Deciphera, EMD Serono, Genentech, Genmab, GSK, Merck, Moderna, The National Cancer Institute, Regeneron, Seagen, and Syros.Dr Powell reports grants/research support from GSK and honoraria/consultation fees from AstraZeneca, Clovis Oncology, Eisai, GSK, Immunogen, and Merck. Dr Gilbert reports institutional grants from Alkermes, GSK, Immunogen Inc, Karyopharm, Merck Sharp & Dohme, Pfizer, Roche, and Tesaro and honoraria/consultation fees from Alkermes, Eisai, Eisai-Merck, GSK, Merck, and Novocure.Dr Mirza reports institutional research grants from Allarity, Apexigen, AstraZeneca, Boehringer Ingelheim, Clovis, GSK, Novartis, and Ultimovacs; trial chair for Deciphera, Mersana, and NuvationBio; invited speaker for AstraZeneca, GenMab, GSK, Mersana, Seagen, and Takeda; a member of board of directors and holds stocks and shares for Karyopharm and Sera Prognostics.Drs Gold, Landrum, Ronzino, Sharma, Wymenga, and Zub have nothing disclose.Drs Antony and Stevens are employees of GSK.

Shoulder instability episodes are observed in high-energy injuries, such as seizures. In this case report, we highlight the management of a failed distal tibial allograft procedure for recurrent shoulder instabilityin a patient with a bony Bankart lesion and epilepsy. The patient was treated with an iliac crest autograft and a proximal humerus osteochondral allograft procedure. To our knowledge, the use of an iliac crest autograft for glenoid bone loss and a proximal humerus osteochondral allograft after several failed shoulder instability procedures in a patient with epilepsy has not been reported.