Long, Kirsten Hall

Abstract In the development of various strategies of anti-CD19 immunotherapy for the treatment of B-cell malignancies, it remains unclear whether CD19 monoclonal antibody therapy impairs subsequent CD19-targeted chimeric antigen receptor T-cell (CART19) therapy. We evaluated the potential interference between the CD19-targeting monoclonal antibody tafasitamab and CART19 treatment in preclinical models. Concomitant treatment with tafasitamab and CART19 showed major CD19 binding competition, which led to CART19 functional impairment. However, when CD19+ cell lines were pretreated with tafasitamab overnight and the unbound antibody was subsequently removed from the culture, CART19 function was not affected. In preclinical in vivo models, tafasitamab pretreatment demonstrated reduced incidence and severity of cytokine release syndrome and exhibited superior antitumor effects and overall survival compared with CART19 alone. This was associated with transient CD19 occupancy with tafasitamab, which in turn resulted in the inhibition of CART19 overactivation, leading to diminished CAR T apoptosis and pyroptosis of tumor cells.

AbstractIntroductionEfforts to model the cost‐effectiveness of managing/modifying cognitive impairment lack reliable, objective, baseline medical, and nursing‐home (NH) costs.MethodsA stratified‐random sample of Olmsted County, MN, residents ages 70–89 years (N = 3545), well‐characterized as cognitively unimpaired, mild cognitive impairment (MCI), or dementia, were followed forward ≤1 year in provider‐linked billing data and the Centers for Medicare & Medicaid Services NH assessments. Direct medical/nursing home/medical + NH costs were estimated. Costs were stratified by vital status and NH‐use intensity (NH days/follow‐up days [0%, 1% to 24%, 25% to 99%, and 100%]). Between‐category mean‐annual cost differences were adjusted for patient characteristics and follow‐up days.ResultsCosts/follow‐up day distributions differed significantly across cognitive categories. Mean costs/follow‐up days were 2.5 to 18 times higher for decedents versus survivors. Among all persons with MCI, <9% with any NH use accounted for 18% of all total annual medical + NH costs. Adjusted‐between‐category comparisons revealed significantly higher medical and medical + NH costs for MCI versus cognitively unimpaired.DiscussionCost‐effectiveness for managing/modifying both MCI and dementia should consider end‐of‐life costs and NH‐use intensity. Results can help inform cost‐effectiveness models, predict future‐care needs, and aid decision‐making by individuals/providers/payers/policymakers.

Background/objectives Objective, complete estimates of nursing home ( NH ) use across the spectrum of cognitive decline are needed to help predict future care needs and inform economic models constructed to assess interventions to reduce care needs. Design Retrospective longitudinal study. Setting Olmsted County, MN . Participants Mayo Clinic Study of Aging participants assessed as cognitively normal ( CN ), mild cognitive impairment ( MCI ), previously unrecognized dementia, or prevalent dementia (age = 70–89 years; N = 3,545). Measurements Participants were followed in Centers for Medicare and Medicaid Services (CMS) Minimum Data Set (MDS) NH records and in Rochester Epidemiology Project provider‐linked medical records for 1‐year after assessment of cognition for days of observation, NH use (yes/no), NH days, NH days/days of observation, and mortality. Results In the year after cognition was assessed, for persons categorized as CN , MCI , previously unrecognized dementia, and prevalent dementia respectively, the percentages who died were 1.0%, 2.6%, 4.2%, 21%; the percentages with any NH use were 3.8%, 8.7%, 19%, 40%; for persons with any NH use, median NH days were 27, 38, 120, 305, and median percentages of NH days/days of observation were 7.8%, 12%, 33%, 100%. The year after assessment, among persons with prevalent dementia and any NH use, >50% were a NH resident all days of observation. Pairwise comparisons revealed that each increase in cognitive impairment category exhibited significantly higher proportions with any NH use. One‐year mortality was especially high for persons with prevalent dementia and any NH use (30% vs 13% for those with no NH use); 58% of all deaths among persons with prevalent dementia occurred while a NH resident. Conclusions Findings suggest reductions in NH use could result from quality alternatives to NH admission, both among persons with MCI and persons with dementia, together with suitable options for end‐of‐life care among persons with prevalent dementia.

Abstract Background Objective cost estimates and source of cost differences are needed across the spectrum of cognition, including cognitively normal (CN), mild cognitive impairment (MCI), newly discovered dementia, and prevalent dementia. Methods Subjects were a subset of the Mayo Clinic Study of Aging stratified‐random sampling of Olmsted County, MN, residents aged 70 to 89 years. A neurologist reviewed provider‐linked medical records to identify prevalent dementia (review date = index). Remaining subjects were invited to participate in prospective clinical/neuropsychological assessments; participants were categorized as CN, MCI, or newly discovered dementia (assessment date = index). Costs for medical services/procedures 1‐year pre‐index (excluding indirect and long‐term care costs) were estimated using line‐item provider‐linked administrative data. We estimated contributions of care‐delivery site and comorbid conditions (including and excluding neuropsychiatric diagnoses) to between‐category cost differences. Results Annual mean medical costs for CN, MCI, newly discovered dementia, and prevalent dementia were $6042, $6784, $9431, $11,678, respectively. Hospital inpatient costs contributed 70% of total costs for prevalent dementia and accounted for differences between CN and both prevalent and newly discovered dementia. Ambulatory costs accounted for differences between CN and MCI. Age‐, sex‐, education‐adjusted differences reached significance for CN versus newly discovered and prevalent dementia and for MCI versus prevalent dementia. After considering all comorbid diagnoses, between‐category differences were reduced (e.g., prevalent dementia minus MCI (from $4842 to $3575); newly discovered dementia minus CN (from $3578 to $711)). Following the exclusion of neuropsychiatric diagnoses from comorbidity adjustment, between‐category differences tended to revert to greater differences. Conclusions Cost estimates did not differ significantly between CN and MCI. Substantial differences between MCI and prevalent dementia reflected high inpatient costs for dementia and appear partly related to co‐occurring mental disorders. Such comparisons can help inform models aimed at identifying where, when, and for which individuals proposed interventions might be cost‐effective.