Real-world Experience Research Articles

Gender differences in the treatment with PCSK9 monoclonal antibodies real world experience from a dedicated prevention clinic

Abstract Background Proprotein convertase subtilisin/kexin type 9 monoclonal antibodies (PCSK9 mAb) lower low-density lipoprotein cholesterol (LDL-C) levels and reduce atherosclerotic cardiovascular disease (ASCVD). There are gender differences in PCSK9 biological characteristics, which are not properly addressed in current data. Purpose Examining gender differences in treatment with PCSK9 mAb. Methods A retrospective study based on data from the Prevention Cardiology Clinic in Rabin Medical Center. Included were patients prescribed with PCSK9 mAb (evolocumab or alirocumab), for primary or secondary prevention. Data included medical background and treatment variables. Response to treatment was evaluated by changes in LDL-C at 3 and 12 months. Data was analyzed by gender. Results Study included 246 patients (mean age 67y, ASCVD 78.8%, mean baseline LDL-C 128.2 mg/dL). Women (42% of cohort) prescribed with PCSK9 mAb were older than men (69 vs. 65 years, respectively; p<0.001). The dominant indication for PCSK9 mAb for both genders was secondary prevention, while primary prevention indication was more prevalent in women vs. men (39.4% vs. 16.3%, respectively; p<0.001). Statin intolerance was observed in 82.4% and 58.6% were treated with combination therapy with PCSK9 mAb, without significant gender differences. Baseline mean LDL-C was higher among women vs. men (138.9 vs. 117.3 mg/dL; p<0.001). Overall, high adherence was observed (91.8% and 79.7% at 3 and 12 months, respectively). After 1-year, adherent men had lower LDL-C levels than women (46.8 mg/d and 61.9 mg/dL, respectively; P=0.001), and were more likely to reach their LDL-C therapy goals; below 70 mg/dL (76.1% vs. 62.2%, respectively; P=0.032) and below 55 mg/dL (60.1% vs. 39.8% respectively; P=0.003). Conclusions In patients treated with PCSK9 mAb, gender differences exist in prescription age, indications, baseline LDL-C and achieved LDL-C goals. In this study adherence to PCSK9 mAb was higher than reported before, possibly due to surveillance in a dedicated prevention clinic.LDL-C & Non-HDL-C levels under PCSK9 mABSex Differences in acheived LDL-C goals

Different treatments in chronic thromboembolic pulmonary hypertension: comparison of strategies in the Italian centre real-world experience

Abstract Rationale Pulmonary endarterectomy (PEA) has been the most effective therapy for chronic thromboembolic pulmonary hypertension (CTEPH). However, there is a substantial proportion of patients declared not operable in whom other treatment strategies are available: medical therapy and balloon pulmonary angioplasty (BPA). We aimed to compare different CTEPH treatment strategies effect in real-world setting. Methods All CTEPH referred to our Centre were included. We compare the short-term clinical, functional, exercise and haemodynamic effect of medical therapy (irrespective of subsequent treatment strategies), PEA and BPA (irrespective of previous/subsequent treatment strategies); we also describe the long-term outcome of the different patient groups. Results We included 467 patients (39% were treated only with medical therapy, 43% underwent PEA, 13% underwent BPA and 5% were not treated with any therapy). Patients treated only with medical therapy were the oldest; compared to patients undergoing PEA, they had a lower exercise capacity, a higher risk profile and gained a lower haemodynamic, functional and survival benefit from the treatment. Patients undergoing BPA had a lower haemodynamic improvement but a comparable functional, exercise and risk improvement and a similar survival compared to patients undergoing PEA; their survival is anyway better than patients undergoing only medical treatment. Untreated historical control patients had the worst survival. Conclusions We confirm the superiority of PEA compared to any alternative treatment in CTEPH and we observe that BPA, in patients declared not operable or with persistent/recurrent PH after PEA, leads to a better outcome than medical therapy alone.

Duties, tasks, knowledge and skills of an obesity medicine physician: A practice analysis

BackgroundGiven the evolving nature of obesity medicine, periodic evaluation of its clinical practice is needed to ensure that certification requirements address real-world experience. Practice analysis is a systematic approach to define a field's body of knowledge, and its results can inform the content outline and examination blueprint for a certification examination. This study describes the 2023 practice analysis conducted by the American Board of Obesity Medicine (ABOM). MethodsInitially, 14 obesity medicine physicians participated in a practice analysis panel, resulting in 3 duties and 30 tasks required for competent practice of obesity medicine physicians. Each task included steps, knowledge, skills, and abilities needed to perform the task. ABOM then recruited 645 certified obesity medicine physicians from its database to participate in a validation survey to rate the frequency [scale: never (0) to very frequently (5)] and importance [scale: not important (0) to very important (3)] of each task. Survey participants could also provide open-ended comments. ResultsAmong validation survey participants (n = 645), the most common primary medical specialties reported were internal medicine (46.0 %), family medicine (33.8 %), and pediatrics (11.2 %). Years practicing obesity medicine varied with 45.3 % reporting 1–4 years, 26.0 % 5–9 years, and 28.7 % ≥ 10 years in practice. Most tasks were performed frequently (mean score ≥4.0) and rated as important (mean score ≥2.0). All tasks were retained based on the frequency and importance ratings. Survey results informed the weighting in the examination blueprint. ConclusionThere was consensus among practicing ABOM-certified physicians who participated in the validation survey in the tasks required for competent obesity medicine practice. Our practice analysis approach was a structured process that engaged obesity medicine physicians and captured the breadth and depth of knowledge required for obesity medicine. The new content outline and examination blueprint developed will be implemented with the 2025 ABOM certification exam administration.

Field Visits as a Pedagogical Tool to Understand Health Determinants

Abstract Background Medical education often focuses on curative medicine, neglecting health determinants. Field visits, common in other educational contexts, enhance understanding of these factors. We aim to offer insights into pedagogical methods applicable to similar educational settings. Objectives Medical students completing an internship at the Gaia-Espinho Public Health Unit participated in field visits to enhance their understanding of health determinants. Guided through two economically distinct areas within a walkable distance of 2km, students documented health determinants through notes and photos. Discussions were held on-site and after visits integrating the real-world experience with theoretical frameworks. An inductive thematic analysis of students’ satisfaction and pedagogical effectiveness of the activity was performed on the internship reports from the 2023/2024 academic year. Results Out of 18 internship reports, 10 described the activity as positive and enriching, of which six highlighted it as a crucial part of the internship. Thirteen reports noted that the activity led to new perceptions about health determinants, and nine highlighted its practical value. Nine students included photos in their reports, bike paths being the most featured. Seventeen provided a clear description and listed the determinants they were able to detect. Discussions highlighted sensory experiences that are uniquely discernible through physical site visits including unpleasant odours, loud noises, and the cooling effect of blue areas on hot days. Three did not provide any evaluative comments, but correctly listed the determinants identified. Conclusions Field visits may enhance medical students’ understanding of health determinants, being recognized as an engaging pedagogical tool. Potential biases in assessments that rely on student satisfaction reports must be considered. Findings support the continuation and expansion of visits in other Public Health internships. Key messages • Field visits, used as a pedagogical tool, may enhance medical students’ ability to understand health determinants. • User Field visits provide a new perspective on previously acquired theoretical knowledge regarding prevention.

Percutaneous decannulation of extracorporeal membrane oxygenation using MANTA device: A real-world single-center experience.

The MANTA vascular closure device (VCD) represents a novel approach to achieving hemostasis after large-bore femoral access procedures. Numerous clinical studies have evaluated the efficacy of the MANTA device across a range of patient populations undergoing different procedures. However, there is still a paucity of data available concerning the use of MANTA devices in aiding the decannulation of venoarterial extracorporeal membrane oxygenation (VA-ECMO). To present our single-center experience of utilizing the MANTA VCD in patients undergoing this procedure. This single-center study included all patients undergoing percutaneous decannulation of femoral VA-ECMO using the MANTA plug-based VCD between January 2021 and October 2023 at University Hospitals Cleveland Medical Center. Inclusion criteria were adult patients who required prolonged (> 24 hours) hemodynamic support with VA-ECMO. Outcomes included all-cause mortality, hemostasis, bleeding, limb ischemia, and site infection. This is a retrospective cohort study of 19 patients with a mean age of 56.8 years. Twelve of them were males with a mean body mass index of 29. The most common extracorporeal membrane oxygenation indication was acute coronary syndrome complicated by cardiogenic shock at 36.8%. The mean length of intensive care unit stay for these patients was 18.8 ± 8.42 days. Seventeen out of 19 patients survived to discharge. The MANTA device was successfully deployed in 19 patients, with 10 procedures conducted at the bedside and 9 in an operating room setting. Complete hemostasis was achieved within 5 minutes of MANTA deployment in 17 out of 19 patients. In 2 patients manual compression after Manta deployment was required to achieve adequate hemostasis. Additionally, acute lower extremity ischemia was noted in two patients, necessitating endovascular interventions. No infections were reported at the site of MANTA deployment. Overall, based on our experience and that of other centers, the MANTA VCD has proven to be a simple, safe, and effective percutaneous technique for facilitating in the OR, but most of all it opens the opportunity for bedside VA-ECMO decannulation. Post-decannulation ischemic complications are higher in this series of sick patients when compared with elective procedures like transcatheter aortic valve replacement and endovascular aneurysm repair. Additionally, operators should be mindful of the incidence of ischemic complications. Distal Doppler pulse signals should always be checked, to indicate bailout options when this occurs.

Long-term Effectiveness and Safety of Risankizumab in Patients with Crohn’s Disease from a Large Tertiary Center

Background and AimsRisankizumab is a selective IL23 inhibitor approved for the treatment of Crohn’s disease (CD). We report a large long-term real-world experience with risankizumab in CD. MethodsWe performed a prospective monitoring of clinical outcomes in patients in our center who started treatment with risankizumab. Patients with active luminal disease who had at least 12 weeks of follow-up were included in the effectiveness analysis. Harvey-Bradshaw Index (HBI) as well as C-reactive protein (CRP) and fecal calprotectin (FCP) were used to monitor disease activity. Primary outcomes were clinical remission and steroid-free clinical remission rates at weeks 12, 26, and 52. Univariate analysis followed by a multivariate analysis using a logistic regression model was performed to identify predictors of steroid-free clinical remission at one year. All patients who started treatment with risankizumab for any indication were included in the safety analysis. Results134 patients were included in the effectiveness analysis. 70 (52%) were ustekinumab-experienced. Clinical remission rates were 69%, 64%, and 54% at weeks 12, 26, and 52, respectively. Steroid-free clinical remission rates at 12, 26, and 52 weeks were 58%, 58%, and 50% respectively. Remission rates in ustekinumab-experienced patients were not statistically lower compared to naïve patients, and in a multivariate analysis, prior ustekinumab treatment was not associated with lower odds of achieving steroid-free clinical remission at one year. Adverse effects were assessed in 243 patients and were consistent with previous literature. ConclusionsThis large real-world experience with risankizumab with long-term follow-up demonstrates effectiveness and safety in patients with CD; there was comparable effectiveness in ustekinumab-naïve and ustekinumab-experienced patients.

Burosumab in adults with X-linked hypophosphatemia: real-world experience from a retrospective study in Sydney

Abstract X-linked hypophosphatemia (XLH) is a chronic disabling hereditary musculoskeletal disorder associated with inactivating PHEX mutations and elevated circulating FGF-23 concentrations. In a placebo-controlled trial of adults with XLH, burosumab (anti-FGF-23 antibody) demonstrated durable improvements in phosphate concentrations, and self-reported stiffness and physical limitation. However, real-world data regarding burosumab efficacy and tolerability in adults with XLH is lacking. A retrospective audit was performed of patients (age ≥ 18-years) who commenced four-weekly subcutaneous burosumab for XLH at Royal North Shore and Westmead Hospitals, Sydney, between January 2021 and June 2024. Patients were managed per standard clinical care and burosumab dose adjusted as necessary according to manufacturer instructions. Electronic medical records were reviewed to collate data regarding patient demographics, XLH-related complications and prior treatment, burosumab dosage and side effects, and pre- and post-burosumab biochemistry and Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores. Of thirteen adults with XLH, all had hypophosphatemia before commencing burosumab (mean 0.64 ± 0.08 mmol/L). Mean WOMAC scores demonstrated baseline impairments in stiffness, pain and physical limitation. Burosumab was administered for median 15 months during follow-up (median dose 70 mg). Hypophosphatemia resolved in all patients within three months of burosumab (mean 1.03 ± 0.38 mmol/L). Two patients developed hyperphosphatemia two weeks after commencing burosumab requiring dose reduction. One patient ceased burosumab in the setting of hypercalcaemia and constipation secondary to pre-existing tertiary hyperparathyroidism. Adverse events were mild, including transient musculoskeletal discomfort (n = 4), restless legs (n = 2), injection site reaction (n = 2) and headache (n = 1). Repeat WOMAC within 12 months of commencing burosumab (n = 9) demonstrated clinically meaningful improvements in stiffness (-33.3 ± 12.5, P<.001) and physical function (-14.3 ± 16.2, P=.029). This study reports real-world outcomes of adults with XLH treated with burosumab. Clinical experience from two centres in Sydney support trial findings that burosumab is well-tolerated and associated with improved serum phosphate concentrations and self-reported stiffness and physical function.

Methods and Techniques to Optimize Energy Delivery Using the Circular Array Pulsed Field Ablation Catheter

Pulsed field ablation (PFA) is a novel method of cardiac ablation in which electrical fields are used to create microscopic pores in the cardiomyocyte cell membrane resulting in cell death. Unlike traditional thermal radiofrequency and cryoablation technologies, PFA is cardiomyocyte preferential, reducing the risk of collateral damage to the esophagus and phrenic nerve. However, achieving durable lesions with PFA is dependent on the proximity to the tissue and presently approved systems do not provide contact force sensing. The PulseSelect pulsed field ablation system is the first FDA approved/ CE marked/PMDA approved system for pulsed field ablation of atrial fibrillation, however there is no consensus on workflow and best practices. We present here real-world experience from our centers in the United States, Europe and Japan, and propose techniques and methods for incorporating fluoroscopy, electro-anatomical mapping, and intracardiac echocardiography to assure optimal lesion delivery and predictability.

Assessing CellaVision peripheral blood and advanced RBC application software's impact on hematologic morphology reporting: Real-world implementation experience in a large Veterans Affairs hospital.

This quality improvement study, conducted at the Kansas City Veterans Affairs Medical Center in Kansas City, Missouri, examined the change in patient reporting after transitioning from manual to CellaVision software-guided differentials and slide reviews. The primary focus was blasts and schistocytes, given their clinical significance. Three months of manual and CellaVision patient data were examined between May 2022 and February 2023. Blast and schistocyte patients were standardized to the total specimens performed and compared using 2-sample proportion testing. Other red blood cell (RBC) morphologies were also compared using this statistical analysis. Blast and schistocyte reporting after technologist review statistically increased after implementing the CellaVision software. This finding was most prevalent for low-percentage blasts. In addition, both morphologies experienced varying degrees of false-positive reporting, with 33% for low-percentage blasts and 91.7% for schistocytes. Other RBC morphologies displayed different levels of change, which could be clinically significant. The CellaVision software's increased sensitivity to blasts and schistocytes may benefit patient care, especially those with hematologic disorders. The software's high false-positive rate can be reduced by implementing quality metrics that prioritize clinically significant cells. This can be accomplished by implementing a CellaVision Champion to monitor reporting changes, perform patient lookbacks through the software, and provide technologist education. In addition, adopting a more stringent grading scale for schistocytes could also improve the high false-positive rate. Overall, CellaVision provides the ability to enhance hematology quality metrics by providing access to how patient cells are categorized and offering prompt education.

Esophagitis and Pneumonitis Related to Concurrent Chemoradiation ± Durvalumab Consolidation in Unresectable Stage III Non-Small-Cell Lung Cancer: Risk Assessment and Management Recommendations Based on a Modified Delphi Process

The addition of durvalumab consolidation to concurrent chemoradiation therapy (cCRT) has fundamentally changed the standard of care for patients with unresectable stage III non-small-cell lung cancer (NSCLC). Nevertheless, concerns related to esophagitis and pneumonitis potentially impact the broad application of all regimen components. A Canadian expert working group (EWG) was convened to provide guidance to healthcare professionals (HCPs) managing these adverse events (AEs) and to help optimize the patient experience. Integrating literature review findings and real-world clinical experience, the EWG used a modified Delphi process to develop 12 clinical questions, 30 recommendations, and a risk-stratification guide. The recommendations address risk factors associated with developing esophagitis and pneumonitis, approaches to risk mitigation and optimal management, and considerations related to initiation and re-initiation of durvalumab consolidation therapy. For both AEs, the EWG emphasized the importance of upfront risk assessment to inform the treatment approach, integration of preventative measures, and prompt initiation of suitable therapy in alignment with AE grade. The EWG also underscored the need for timely, effective communication between multidisciplinary team members and clarity on responsibilities. These recommendations will help support HCP decision-making related to esophagitis and pneumonitis arising from cCRT ± durvalumab and improve outcomes for patients with unresectable stage III NSCLC.

Real-World Experience Of The Association of HLADQA1*05 Allele with Loss of Response to Anti-TNF Inhibitors

Abstract Goals and Background Anti–tumor necrosis factor (anti-TNF) biologics have revolutionized the treatment of inflammatory bowel disease (IBD). Previously, studies have shown an association between the HLADQA1*05 allele and the development of antibodies and was predictive of loss of response. We sought to investigate the rate of the HLADQA1*05 allele in patients with IBD at a New England center and its association with antibody development and discontinuation of anti-TNF therapy. Study A single center retrospective cohort study with patients on anti-TNF inhibitor therapy being followed at our IBD clinic who had testing performed for the HLADQA1*05 allele were identified and separated into two different groups: HLADQA1*05 positive (HLA-carriers) or HLADQA1*05 negative (HLA non-carriers). Persistence of remaining on anti-TNF therapy, measurement of drug/antibody levels, and need for dose escalation was collected and stratified amongst the two groups. Results The prevalence of the HLADQA1*05 allele among all IBD patients followed was 53%. We identified 67 IBD patients being treated with anti-TNF medications, 46 (69%) patients with Crohn’s disease and 21 (31%) with ulcerative colitis. Most of the HLA carriers (85%) and HLA non-carriers (92%) remained on anti-TNF therapy at the end of the study period. 36 (84%) patients had therapeutic drug monitoring performed during maintenance therapy. Three patients in the HLA carrier group had meaningful anti-drug antibody levels necessitating cessation of therapy compared to one patient in the HLA non-carrier group (p = 0.61). Only 3 (13%) of HLA carriers and 4 (21%) of HLA non-carriers were on combination therapy with an immunomodulator. 65% of HLA carriers required dose escalation compared to 50% of HLA non-carriers (p= 0.70). Conclusion The prevalence of the HLADQA1*05 allele was 53% in our New England IBD patient population, similar to what has previously been reported in European studies. The majority of patients remained on anti-TNF therapy at the end of the study period despite carrier status. While there was a trend toward increased need for dose escalation among HLA carriers, this was not statistically significant. Future studies are needed to determine if the presence of the HLADQA1*05 allele leads to the antibody development against anti-TNF inhibitors and treatment failure in patients with IBD.

Evaluation and real-world experience of a neutralization susceptibility screening assay for broadly neutralizing anti-HIV-1 antibodies.

Development of a screening assay for the clinical use of broadly neutralizing antibodies (bnAbs) is a priority for HIV therapy and cure initiatives. We assessed the PhenoSense Monoclonal Antibody (mAb) Assay (Labcorp-Monogram Biosciences) which is CLIA-validated and has been used prospectively and retrospectively in multiple recent bnAb clinical trials. When performed on pre-ART plasma and on-ART longitudinal PBMC samples sourced from a recent clinical trial, the PhenoSense mAb Assay produced robust reproducibility, concordance across sample types, and expected ranges in the susceptibility measures of bnAbs in clinical development. PhenoSense mAb applied retrospectively to baseline samples from three recent studies correlated with published laboratory-based study evaluations, but baseline bnAb susceptibility was not consistently predictive of durable virus suppression. Assessment of the feasibility of the assay in four recent clinical studies provides estimates of assay success rate and processing time. The PhenoSense mAb Assay provides reproducible bnAb susceptibility measurements across relevant sample types yet was not consistently predictive of virus suppression. Logistical and operational assay requirements can impact timely clinical trial conduct. These results inform bnAb studies in development.

Opportunities Behind Challenges for Classroom Management at Aisyiyah Kindergarten in Kalitengah Village

Community Service Program (KKN) is an extracurricular activity that combines the Tri Dharma of Higher Education, as well as learning and community service. This course is designed to provide students with real-world experience while also enhancing their critical thinking skills. KKN focuses on community welfare. This article discusses the implementation of the 2024 KKN-T group 23 in Kalitengah Village, Tanggulangin, focusing on the educational aspect. This study examines the challenges of teaching in the Aisyiyah Kindergarten class in Kalitengah Village and explores the innovative opportunities that arise from this situation. With an unfavorable teacher-to-student ratio, this educational institution faces several challenges in providing high-quality education. Using qualitative research methods, this study examines the adaptive strategies developed by students and teachers. Data was collected through participatory observation, interviews with teachers and school principals, as well as analysis of school documents. The main idea is that the lack of human capital has driven the implementation of more collaborative and creative learning methods. Strategies such as the implementation of a peer mentoring system, integration of educational technology, and active involvement of parents in the learning process have produced unexpectedly positive outcomes. The research results indicate an increase in student independence, better development of social-emotional skills, as well as efficiency in time and resource management. This study concludes that challenges can serve as a catalyst for educational innovation, with important implications for the development of adaptive and effective classroom management models in other early childhood education institutions facing similar limitations.

Gene therapy in transfusion-dependent non-β0/β0 genotype β-thalassemia: first real-world experience of beti-cel

AbstractGene addition and editing strategies for transfusion-dependent β-thalassemia have gained momentum as potentially curative treatment options, with studies showcasing their efficacy and safety. We report, to our knowledge, the first real-world application of betibeglogene autotemcel (beti-cel; Zynteglo) during its period of active license in Europe from January 2020 to March 2022 for patients aged ≥12 years without a β0/β0 genotype and without a HLA-matched sibling donor, before beti-cel marketing authorization was withdrawn by its holder because of nonsafety reasons. Among 15 screened patients, 4 opted out for fertility and safety concerns, 2 were excluded because of marked hepatic siderosis, and 1 had apheresis collection failure. Eight patients received beti-cel after busulfan myeloablative conditioning, all achieving transfusion independence within 8 to 59 days, with posttreatment hemoglobin levels ranging from 11.3 to 19.3 g/dL. No deaths occurred, but acute toxicity mirrored busulfan’s known effects. Posttreatment platelet management faced challenges because of HLA-antibodies in 3 patients. Monitoring up to month 24 revealed pituitary-gonadal endocrine dysfunction in all 3 female and in 2 of 5 male patients. Additionally, we observed unexpected posttreatment sequelae: 1 patient developed polycythemia that could not be explained by known genetic or acquired mechanisms, 1 patient developed posttreatment depression and anxiety prohibiting her from returning to work, and 1 patient developed fatigue severely compromising both quality of life and work capacity. This real-world experience corroborates beti-cel’s efficacy and safety and provides information on adverse events observed during real-world use of the therapy.

Real-World Experience of Erenumab in Patients with Migraine in Germany: The SPECTRE Study.

To provide real-world insights into migraine patient population in Germany treated with erenumab, focusing on the prescription patterns and reasons for the initial dosage choice. SPECTRE was an observational, non-interventional, multicenter, open-label, single-arm study in patients treated with erenumab according to approved local dose and guidelines. The study enrolled adult patients (n = 571; Germany: 105 sites) with migraine who had received erenumab for not more than 3months before the start of the study. The mean (standard deviation) patient age was 45.0 (12.3) years, and most patients were female (89.0%), Caucasian (97.6%), and non-smokers (85.1%). The starting dose of erenumab was 70mg in 68.5% of patients and 140mg in 31.5%. The proportion of patients with 140mg as the starting dose was the highest (43.5%) in those aged 30-40years. The most common reason for starting a higher dose of erenumab 140mg was severity of migraine (47.4%). During the observational period, the proportion of patients taking erenumab 140mg increased to 64.6% (visit 5; V5) after 12months. Due to attrition of patients towards the end of the study (V9: 90 participants), data at V9 must be interpreted with caution. At least one dose change was performed in 45.3% of patients (i.e., erenumab 70 to 140mg or 140 to 70mg), 21.2% of patients attempted at least once to discontinue treatment (i.e., period with erenumab discontinuation and no other antibody treatment for migraine prevention), and 15.3% discontinued erenumab treatment, mainly because of no or insufficient treatment response (13.5%). The mean time until the first omission attempt was 332.3 (range 37-633) days. Constipation (12.1%) was the most frequently reported adverse event, in line with the summary of product characteristics (SmPC) of erenumab. Most patients with migraine were prescribed erenumab 70mg as the starting dose. No new safety signals were observed for erenumab versus the previous trials.

Impact of Allogeneic Stem Cell Transplant on Safety and Outcomes of Chimeric Antigen Receptor T Cell (CAR-T) Therapy in Patients with Multiple Myeloma (MM).

Background: Allogeneic stem cell transplantation (allo-SCT) has seen limited use in treating multiple myeloma (MM), despite its potential to offer long-term survival or even cure through the graft-versus-myeloma effect. Its limited application is largely due to concerns over serious complications like infections and graft-versus-host disease (GVHD). The possibility of GVHD exacerbation when CAR-T cells are administered to patients previously treated with allo-SCT remains a topic of concern. Ciltacabtagene autoleucel (Cilta-cel) and idecabtagene vicleucel (Ide-cel) are CAR-T therapies that have been FDA-approved for relapsed/refractory (R/R) MM. A recent study using data from the CARTITUDE-1 trial has shown promising safety and efficacy of Cilta-Cel in patients with a prior history of allo-SCT. This report outlines our real-world experience with CAR-T treatment in such patients. The objective of this study is to assess the safety and effectiveness of CAR-T therapy in R/R MM patients who have previously undergone allo-SCT. Methods: We conducted a retrospective analysis of adult patients (18-70 years old) with R/R MM treated with CAR-T therapy as part of an institutional IRB-approved protocol. Data were collected on safety and efficacy outcomes from the institution's records. Adverse events (AEs) were evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were graded based on American Society for Transplantation and Cellular Therapy (ASTCT) criteria. Efficacy metrics included overall response rate (ORR) and progression-free survival (PFS), analyzed through the Kaplan-Meier method, with PFS defined as the time from CAR-T initiation to disease progression or death. Results: Of the 56 patients treated with CAR-T therapy, 8 (14.3%) had previously undergone allo-SCT. These patients had a median of seven prior therapy lines (LOTs), compared to five LOTs in the non-allo-SCT group (p = 0.04). CAR-T infusion occurred a median of 98.8 months after allo-SCT, with a range from 57.9 months to 178.5 months. CRS occurred in 87.5% of the allo-SCT group versus 77.1% in the non-allo-SCT group (p = 0.48). One patient in the allo-SCT group developed hemophagocytic lymphohistiocytosis (HLH), requiring anakinra. At a median follow-up of 4.8 months, the ORR was 87.5% in the allo-SCT group versus 75% in the non-allo-SCT group (p = 0.4). Median PFS had not been reached for the allo-SCT group at the time of analysis compared to 11.9 months in the non-allo-SCT group (p = 0.5). No treatment-related mortality or acute GVHD was noted in the allo-SCT cohort. Conclusions: The study suggests that prior allo-SCT does not adversely affect the safety or efficacy of CAR-T therapy in patients with R/R MM. These findings highlight the need for further investigations with larger patient samples and longer follow-up to better understand the interaction between allo-SCT and CAR-T therapy.

Real-world experience of emicizumab prophylaxis in Korean children with severe hemophilia A without inhibitors

PurposeHemophilia A is a genetic disorder characterized by a lack of factor VIII (FVIII). Emicizumab, a recombinant humanized bispecific monoclonal antibody, mimics the function of FVIII. In this article, we present data on an initial real-world evaluation of emicizumab use in Korean children with severe hemophilia A without inhibitors.MethodsThis study was conducted from June 2020 to March 2024 at 4 centers in Korea. The participants were pediatric patients with severe hemophilia A without inhibitors who had received emicizumab treatment for over 6 months. The mean and median annualized bleeding rates (ABRs) and mean and median annual joint bleeding rates (AJBRs) were compared.ResultsEach of the 21 patients in the study received an emicizumab loading regimen of 3 mg/kg weekly for 4 weeks, followed by a modified maintenance regimen of which 2 patients (9.5%) received a 1.5 mg/kg weekly dose, 3 patients (14.3%) received a 6 mg/kg dose every 4 weeks, and the remaining 16 patients (76.2%) received a 3 mg/kg dose every 2 weeks. Before emicizumab prophylaxis initiation, the mean and median ABRs for all patients were 7.04 (SD ± 5.83) and 6.52 (range 0–21.74), respectively. After receiving emicizumab treatment, the mean and mediam ABRs decreased to 0.41 and zero, respectively. Additionally, 85.7% of the patients achieved no bleeding events within 6 months of starting the treatment.ConclusionThese first real-world data in Korea indicate that emicizumab is effective and safe for pediatric patients with severe hemophilia A without inhibitors.

Total Neoadjuvant Therapy in Locally Advanced Rectal Cancer: Insights from the Western Australian Context.

Recent studies have associated total neoadjuvant therapy (TNT) with better treatment adherence, decreased toxicity, improved complete clinical response and anal sphincter preservation rates in patients with locally advanced rectal cancer (LARC). However, real-world experience with TNT in the management of LARC remains limited. This study aimed to evaluate the efficacy and safety outcomes of TNT for LARC in Western Australia. Patients with LARC (cT2-4 and/or cN1-2) who underwent induction chemotherapy followed by neoadjuvant chemoradiotherapy or neoadjuvant chemoradiotherapy followed by consolidation chemotherapy, followed by surgery were recruited from two hospitals in Western Australia. Efficacy outcomes assessed included clinical response (complete, partial, no response), and pathologic complete response (pCR) rate, R0 resection rate, and R1 resection rate were evaluated. Those patients who achieved clinical complete response following TNT were given the option of active surveillance. The safety and tolerability of TNT were assessed. 32 patients with LARC were treated with TNT. In total, 17 patients (53%) received chemoradiotherapy followed by consolidation chemotherapy and 15 patients (47%) received induction chemotherapy followed by chemoradiotherapy. Nine (28%) of the patients with LARC treated with TNT had a complete clinical response, twenty-one (66%) patients had a partial clinical response, and two (6%) patients had no response to TNT. Of the 32 patients, 27 (84%) underwent surgery. There was a 100% R0 resection rate. The pCR rate was 15%. pCR, clinical response, and the R0 resection rate were similar between the two TNT regimens. TNT was well tolerated, with the majority of patients (88%) completing the chemotherapy course with grade 1 and 2 adverse effects. In conclusion, TNT emerges as a promising approach for the management of LARC. However, further research is warranted to refine the optimal TNT protocols, determine its long-term outcomes, and identify patient populations who would benefit the most from this innovative therapeutic strategy.

Expert opinion on candidacy for bone conduction hearing implants Osia System and Baha Connect System.

<b>Introduction:</b> Bone conduction hearing implants (BCHI) are a widely used rehabilitation solution for patients with conductive hearing loss (CHL), mixed hearing loss (MHL), or single-sided deafness (SSD).<b>Aim:</b> This expert review presents candidacy criteria considerations when choosing between active transcutaneous bone-conduction hearing devices (Osia<sup></sup> System) and passive percutaneous bone-conduction hearing devices (Baha<sup></sup> Connect System) to help streamline the decision-making process in those contexts where economics have a major impact on professionals' and patients' choice.<b>Methods:</b> Eight experts participated in two online surveys and two virtual meetings to discuss real-world clinical experience to highlight treatment approaches and factors considered when counseling the patients and selecting an optimal BCHI solution. Key considerations for decision-making were recorded following consensus from all experts.<b>Conclusions:</b> Aspects in decision making include the requirement to use local <i>versus</i> general anesthesia for the implantation procedure, bone thickness, considerations for future magnetic resonance imaging (MRI) procedures, and patient preference. Increased risk of skin infections, requirements for cleaning and managing the implant site, particularly for those with limited dexterity, as well as esthetic concerns could make the Baha<sup></sup> Connect System unsuitable for some patients. In these cases, the Osia<sup></sup> System may provide clear advantages, particularly in patients for whom good hearing performance is a priority, and this would need to be discussed individually with the patient in a multidisciplinary setting. Conversely, for patients requiring minimally invasive surgery, who have contraindications for general anesthesia or require frequent head MRI scans in the future, the Baha Connect System may be more suitable.

P2.14A.02 Assessment of Immunohistochemical Panel Utilization in Thymic Carcinoma Diagnosis: Real World Experience Insights

P2.14A.02 Assessment of Immunohistochemical Panel Utilization in Thymic Carcinoma Diagnosis: Real World Experience Insights