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Introduction Talquetamab (Tal) is a bispecific antibody therapy approved for patients with relapsed/refractory multiple myeloma (MM), targeting both GPRC5D x CD3 receptors. Clinical studies demonstrate that Tal creates deep and durable responses, but less is known about the patient experience. This study aimed to explore the experiences of patients from the patient and physician perspectives to help understand what to expect with this first-in-class novel therapy. Methods This qualitative study consisted of two components. First, patients with documented use of Tal were identified and recruited through the HealthTree Cure Hub. Individual patients then took part in 2-hour, semi-structured virtual interviews. Patients were asked to discuss their experiences 1-2 months prior to starting Tal and 4-5 months after beginning therapy. Patients discussed GPRC5D-related symptoms (including oral, skin-related, and nail-related symptoms), overall impact, and satisfaction. Participants were US adults diagnosed with MM who took Tal for at least 4 months, either in a clinical trial or commercial setting. Interviews were conducted February-April 2024. Second, patients and physicians gathered in a facilitated roundtable discussion to review findings and generate ideas for symptom management. The roundtable lasted 2.5 hours and took place in Chicago, IL in May 2024. Results Eight men and 4 women (n=12) aged 52-79 years participated in the interviews. Interviewed participants were mostly white (84%) and college-educated (84%). Seven (58%) received Tal in a clinical trial, and 9 were still receiving Tal. Roundtable participants included 3 patients (2 male, 1 female; all white and college educated), and 3 physicians with Tal experience. In the interviews, patients reported high overall satisfaction, with most (75%) rating their satisfaction an 8 or higher on a 10-point scale. Satisfaction was largely driven by the effectiveness of therapy, with all reporting clinical improvements in their MM disease. Patients reported improvements in their energy/strength and decreased fatigue. They also reported increased physical activities and ability to work, volunteer, or engage in hobbies. Physicians affirmed these findings as consistent with their observations and noted they are also very satisfied with Tal. Oral symptoms such as distorted taste/loss of taste and dry mouth were common with varying severity. Although all interviewees (n=12) reported taste symptoms (typically starting within the first month of therapy), five said their symptoms fully improved (3 after 1 year on treatment, and 2 after stopping treatment), and 4 experienced partial recovery. Ten lost weight, but most (92%) maintained adequate nutrition. Patients and physicians suggested coping strategies including diet modifications, use of strong flavors (e.g., spices, cinnamon), monitoring weight, prioritizing adequate calories, using mouthwashes/lozenges, drinking water while eating, taking small bites, and consuming foods that are easier to swallow. They also noted that it is important to educate patients on expected symptoms before starting the treatment. Skin- and nail-related symptoms were also common but less impactful on quality of life. All patients (n=12) experienced skin- and nail-related symptoms, but most considered these symptoms mild. Skin-related symptoms such as dry skin and skin exfoliation occurred once and typically lasted 1-2 months. Nail symptoms were primarily cosmetic, and the duration varied. Suggested management strategies include skin moisturizers, nail thickeners/hardeners, keeping nails short, and wearing protective gloves. Physicians noted it's helpful to reassure patients that nail loss is not harmful. Overall, GPRC5D-related symptoms were not treatment-limiting, and no patients had to miss a dose due to these symptoms. Patients perceived these symptoms as bearable but noted the treatment was effective at controlling the disease. Conclusions This study described patient experiences and reflected how patients perceive the benefit/risk profile of talquetamab. Symptoms were perceived as bearable and high satisfaction scores were driven by strong clinical effectiveness. Patients and physicians agreed that real-world feedback from patients, practical tips, and management strategies are vitally important for patients and physicians using this novel therapy.

ImportanceIncreased white matter hyperintensity (WMH) volume is a common magnetic resonance imaging (MRI) finding in both autosomal dominant Alzheimer disease (ADAD) and late-onset Alzheimer disease (LOAD), but it remains unclear whether increased WMH along the AD continuum is reflective of AD-intrinsic processes or secondary to elevated systemic vascular risk factors.ObjectiveTo estimate the associations of neurodegeneration and parenchymal and vessel amyloidosis with WMH accumulation and investigate whether systemic vascular risk is associated with WMH beyond these AD-intrinsic processes.Design, Setting, and ParticipantsThis cohort study used data from 3 longitudinal cohort studies conducted in tertiary and community-based medical centers—the Dominantly Inherited Alzheimer Network (DIAN; February 2010 to March 2020), the Alzheimer’s Disease Neuroimaging Initiative (ADNI; July 2007 to September 2021), and the Harvard Aging Brain Study (HABS; September 2010 to December 2019).Main Outcome and MeasuresThe main outcomes were the independent associations of neurodegeneration (decreases in gray matter volume), parenchymal amyloidosis (assessed by amyloid positron emission tomography), and vessel amyloidosis (evidenced by cerebral microbleeds [CMBs]) with cross-sectional and longitudinal WMH.ResultsData from 3960 MRI sessions among 1141 participants were included: 252 pathogenic variant carriers from DIAN (mean [SD] age, 38.4 [11.2] years; 137 [54%] female), 571 older adults from ADNI (mean [SD] age, 72.8 [7.3] years; 274 [48%] female), and 318 older adults from HABS (mean [SD] age, 72.4 [7.6] years; 194 [61%] female). Longitudinal increases in WMH volume were greater in individuals with CMBs compared with those without (DIAN: t = 3.2 [P = .001]; ADNI: t = 2.7 [P = .008]), associated with longitudinal decreases in gray matter volume (DIAN: t = −3.1 [P = .002]; ADNI: t = −5.6 [P < .001]; HABS: t = −2.2 [P = .03]), greater in older individuals (DIAN: t = 6.8 [P < .001]; ADNI: t = 9.1 [P < .001]; HABS: t = 5.4 [P < .001]), and not associated with systemic vascular risk (DIAN: t = 0.7 [P = .40]; ADNI: t = 0.6 [P = .50]; HABS: t = 1.8 [P = .06]) in individuals with ADAD and LOAD after accounting for age, gray matter volume, CMB presence, and amyloid burden. In older adults without CMBs at baseline, greater WMH volume was associated with CMB development during longitudinal follow-up (Cox proportional hazards regression model hazard ratio, 2.63; 95% CI, 1.72-4.03; P < .001).Conclusions and RelevanceThe findings suggest that increased WMH volume in AD is associated with neurodegeneration and parenchymal and vessel amyloidosis but not with elevated systemic vascular risk. Additionally, increased WMH volume may represent an early sign of vessel amyloidosis preceding the emergence of CMBs.

PURPOSE: Median duration of daratumumab (DARA) administration for treatment of multiple myeloma is 3-7 hours for the intravenous formulation (DARA IV) and 3-5 minutes for the subcutaneous formulation (DARA SC). Here, we describe clinical administration characteristics of DARA using a novel method for data extraction from electronic health records. METHODS: Time-based measurements were extracted using a scheduling/pharmacy software program that tracked patient movement through appointments for patients initiating DARA in Mayo Clinic infusion centers from April 5, 2017, to October 14, 2021. Cohorts included patients who received DARA IV or DARA SC, or converted from DARA IV to DARA SC. The DARA SC cohort was further analyzed before (DARA SC initial) and after (DARA SC shortened) a reduction in the postadministration observation time mandated by the treatment plan. Events associated with administration-related reactions (ARRs) were also identified. RESULTS: Median total clinic times were 2.7-3.0 hours shorter for DARA SC versus DARA IV. Median clinic times were highest at dose 1 and decreased with subsequent doses. Median total chair times were 2.7-2.8 hours shorter for DARA SC versus DARA IV. Incidences of ARR-related events with DARA SC were low across doses. CONCLUSION: Reduced clinic times were observed with DARA SC, indicating that use of DARA SC as a treatment option results in time savings that may free clinic resources. Furthermore, novel methods of electronic health record data extraction can provide insights that may help inform clinic resource optimization.

ImportanceThere is limited evidence for therapeutic options for pediatric COVID-19 outside of multisystem inflammatory syndrome in children (MIS-C).ObjectiveTo determine whether the use of steroids within 2 days of admission for non–MIS-C COVID-19 in children is associated with hospital length of stay (LOS). The secondary objective was to determine their association with intensive care unit (ICU) LOS, inflammation, and fever defervescence.Design, Setting, and ParticipantsThis cohort study analyzed data retrospectively for children (<18 years) who required hospitalization for non–MIS-C COVID-19. Data from March 2020 through September 2021 were provided by 58 hospitals in 7 countries who participate in the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS) COVID-19 registry.ExposureAdministration of steroids within 2 days of admission.Main Outcomes and MeasuresLength of stay in the hospital and ICU. Adjustment for confounders was done by mixed linear regression and propensity score matching.ResultsA total of 1163 patients met inclusion criteria and had a median (IQR) age of 7 years (0.9-14.3). Almost half of all patients (601/1163, 51.7%) were male, 33.8% (392/1163) were non-Hispanic White, and 27.9% (324/1163) were Hispanic. Of the study population, 184 patients (15.8%) received steroids within 2 days of admission, and 979 (84.2%) did not receive steroids within the first 2 days. Among 1163 patients, 658 (56.5%) required respiratory support during hospitalization. Overall, patients in the steroids group were older and had greater severity of illness, and a larger proportion required respiratory and vasoactive support. On multivariable linear regression, after controlling for treatment with remdesivir within 2 days, country, race and ethnicity, obesity and comorbidity, number of abnormal inflammatory mediators, age, bacterial or viral coinfection, and disease severity according to ICU admission within first 2 days or World Health Organization ordinal scale of 4 or higher on admission, with a random intercept for the site, early steroid treatment was not significantly associated with hospital LOS (exponentiated coefficient, 0.94; 95% CI, 0.81-1.09; P = .42). Separate analyses for patients with an LOS of 2 days or longer (n = 729), those receiving respiratory support at admission (n = 286), and propensity score–matched patients also showed no significant association between steroids and LOS. Early steroid treatment was not associated with ICU LOS, fever defervescence by day 3, or normalization of inflammatory mediators.Conclusions and RelevanceSteroid treatment within 2 days of hospital admission in a heterogeneous cohort of pediatric patients hospitalized for COVID-19 without MIS-C did not have a statistically significant association with hospital LOS.

Abstract Introduction: Daratumumab is approved across lines of therapy for multiple myeloma (MM) by subcutaneous administration (DARA SC) or by intravenous administration (DARA IV). In clinical studies, the administration time ranges from 3-5 minutes for DARA SC versus 3-7 hours for DARA IV, and DARA SC is associated with reduced rates of administration-related reactions (ARRs). These characteristics of DARA SC are associated with benefits for clinics in terms of safety and clinic time. We previously reported DARA administration characteristics at Mayo Clinic infusion centers: DARA SC had shorter total clinic and total chair times compared with DARA IV, and DARA SC was associated with very low rates of ARR-related events (Soefje S, et al. EHA Library. 2021). Based upon this analysis, the treatment plan was modified to reduce the mandated observation time for DARA SC to improve clinic efficiency. Here, we describe updated clinical administration characteristics for DARA SC at Mayo Clinic infusion centers before and after the reduction in procedure-mandated observation time, versus DARA IV, using a novel empirical data extraction approach from Electronic Health Records (EHR). Methods: Patients ≥18 years of age with an ICD-9/10 diagnosis code of MM and a first DARA treatment between April 5, 2017 and June 22, 2021 were identified in Mayo Clinic's EHR database. Data were extracted using a scheduling and pharmacy software that tracked patient movement through appointments at a Mayo Clinic infusion center. On May 3, 2021, the Mayo treatment plan was amended to shorten the mandated post-administration observation time for DARA SC from 4 to 2 hours for Dose 1 and from 1 hour to 30 minutes for Doses 2 and 3, with no mandated observation time for Doses 4+. In this analysis, data were captured for patients initiating DARA IV throughout the defined treatment window. For DARA SC, data were captured for patients starting DARA SC therapy on the initial treatment plan (before May 3, 2021; DARA SC initial) and after the change to shorten the mandated post-administration observation time for DARA SC (after May 3, 2021; DARA SC shortened). Time-based measures included: total clinic time (check-in time through patient check-out); total chair time (time from infusion room entry to infusion room exit or check-out time, including order review, pharmacy preparation time, and post-administration observation time); and observation time (time from the end of medication administration to infusion room exit or patient check-out). The medication administration time documented for DARA SC was 0 minutes due to the default duration for SC injections in the EHR. Results: In total, 755 (DARA IV, n=586; DARA SC initial, n=145; DARA SC shortened, n=24) patients received DARA treatment for MM. For all doses combined, the median total clinic time was 2.9 hours shorter for DARA SC compared with DARA IV (DARA IV, 4.9 hrs; DARA SC initial, 2.0 hrs). The median total clinic time for DARA SC and DARA IV was highest at Dose 1 (DARA IV, 9.5 hrs; DARA SC initial, 6.1 hrs; DARA SC shortened, 4.4 hrs) and lower for subsequent doses (Dose 4+: DARA IV, 4.6 hrs; DARA SC initial, 1.7 hrs; DARA SC shortened, 1.6 hrs; Figure). Similarly, the median total chair time was 2.7 hours shorter in the DARA SC group compared with the DARA IV group for all doses combined (DARA IV, 4.1 hrs; DARA SC initial, 1.4 hrs). The median total chair time for DARA SC and DARA IV was highest at Dose 1 (DARA IV, 8.8 hrs; DARA SC initial, 5.6 hrs; DARA SC shortened, 3.9) and lower for subsequent doses (Dose 4+: DARA IV, 3.7 hrs; DARA SC initial, 1.1 hrs; DARA SC shortened, 1.1 hrs). Conclusion: Marked reductions in the amount of time spent both in clinic and in chair were observed with DARA SC compared with DARA IV, with additional time savings observed following the Mayo procedure change to reduce the DARA SC mandated observation time. These favorable DARA SC administration characteristics may indicate a reduction in the burden on both clinical resources and patients in Mayo Clinic infusion centers. These results add to the growing body of evidence supporting the use of DARA SC as an efficient and convenient treatment administration option for patients with MM. Figure 1 Figure 1. Disclosures Soefje: Beigene: Consultancy; Pfizer: Speakers Bureau; Janssen: Consultancy, Research Funding. Carpenter: nference Inc.: Current Employment; Janssen: Consultancy. Carlson: nference Inc.: Current Employment; Janssen: Consultancy. Awasthi: nference Inc.: Current Employment, Current holder of individual stocks in a privately-held company; Janssen: Consultancy. Lin: Janssen: Current Employment. Kaila: Janssen Scientific Affairs, LLC: Current Employment. Kayal: nference Inc.: Current Employment; Janssen: Consultancy. Kirkup: nference Inc.: Current holder of individual stocks in a privately-held company, Ended employment in the past 24 months; Path AI: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Wagner: nference Inc.: Current Employment; Janssen: Consultancy. Gray: Janssen Scientific Affairs, LLC: Current Employment, Current holder of individual stocks in a privately-held company. Kumar: Oncopeptides: Consultancy; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Carsgen: Research Funding; Antengene: Consultancy, Honoraria; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Research Funding; Astra-Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding; Bluebird Bio: Consultancy; Beigene: Consultancy; Tenebio: Research Funding; Roche-Genentech: Consultancy, Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Research Funding.

617 Background: Over the past decade, seven agents were approved for metastatic renal cell carcinoma (mRCC) leading to a rapidly evolving clinical landscape. Clinical trials addressing treatment efficacy, sequencing, and other questions may continue to impact management decisions. Furthermore, our prior retrospective experience indicates a significant proportion of pts may not receive systemic therapy in the first year after diagnosis with metastatic disease. This analysis describes contemporary patterns of care in the first 109 real world pts enrolled in a multicenter, prospective, observational registry. Methods: MaRCC Registry will enroll 500 pts from up to 60 US academic (ACAD) and community (COMM) sites with ~2 years of recruitment and ≥ 3 years of follow-up. Key inclusion criteria are age ≥ 18 years and diagnosis of mRCC with no prior systemic therapy (STx) for mRCC at study entry. Pts currently not on STx but who are being observed are permitted. Key endpoints include descriptive characteristics of treatments (e.g. treatment agents, sequence, duration, reasons for therapy choice and discontinuation), treatment effectiveness (e.g. overall response rate, progression free survival, overall survival), quality of life (PROs), medication adherence, and health resource utilization. Results: At data cutoff, 105 pts have been accrued with known STx status; median age 64 (Q1-3 range, 56-70); 66% male; 75% ACAD; 87% clear cell histology; and 31% stage IV at diagnosis. Initial management strategies are shown in the table. The initial management decision after accrual was to defer systemic therapy (Def STx) in 40% (N=44). In ACAD and COMM sites, Def STx percentages were 38% and 48% respectively. Baseline demographics and clinical characteristics were not notably different between Def STx pts and those treated with STx. Conclusions: In our prospective registry, we have identified a large percentage of pts who initially received Def STx. In the context of contemporary pts undergoing investigational and standard of care STx, we will describe the management and outcomes of the Def STx population. [Table: see text]

563 Background: Clinical trials mRCC pts are different from real world pts, resulting in bias in the literature. The MaRCC Registry is designed to survey questions not asked in tri als, such as why physicians make certain management decisions. This analysis describes reasons for physician treatment (tx) selection in the first 109 real world pts enrolled in a multicenter, prospective, observational registry. Methods: MaRCC Registry will enroll 500 pts from up to 60 US academic (ACAD) and community (COMM) sites with ~2 years of recruitment and ≥ 3 years of follow-up. Key inclusion criteria are age ≥ 18 years and diagnosis of mRCC with no prior systemic therapy (STx) for mRCC at study entry. Pts currently not on STx but who are being observed are permitted. Key endpoints include descriptive characteristics of txs, tx and patient outcomes, medication adherence, and health resource utilization. Results: At data cutoff, 105 pts have been accrued with known STx status; median age 64 (Q1-3 range, 56-70); 66% male; 75% ACAD; 87% clear cell histology; and 31% stage IV at diagnosis. Initial management decision was: 40% deferred systemic therapy (DSTx), 22% pazopanib, 18% clinical trial, 10% sunitinib, and 6% other. Among STx pts (N = 61), the most common categories for therapy choice as selected by providers were likelihood of clinical benefit (41%) followed by pt characteristics (30%). Within the clinical benefit category, the most common reason was OS/PFS (31%). Within the pt characteristic category the most common reasons included performance status/frailty (12%) or prognostic factors (12%). Common reasons for DSTx pts (N = 44) were active surveillance (AS) with disease present (39%), AS without disease present following a procedure (11%), or local therapy (7%). ACAD sites had higher percentages of pts with DSTx undergoing AS with disease present and local therapy. Conclusions: This is the first report describing factors driving physician decision making in management of mRCC. Management choices are not captured in other prospective or retrospective studies. Early experience suggests that clinical benefit and pt characteristics were common reasons for initial STx. Side effect profile rarely determined initial STx selection.