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Alzheimer's disease (AD) continuum is defined as a cascade of several neuropathological processes that can be measured using biomarkers, such as cerebrospinal fluid (CSF) levels of Aß, p-tau, and t-tau. In parallel, brain anatomy can be characterized through imaging techniques, such as magnetic resonance imaging (MRI). In this work we relate both sets of measurements and seek associations between biomarkers and the brain structure that can be indicative of AD progression. The goal is to uncover underlying multivariate effects of AD pathology on regional brain morphological information. For this purpose, we used the projection to latent structures (PLS) method. Using PLS, we found a low dimensional latent space that best describes the covariance between both sets of measurements on the same subjects. Possible confounder effects (age and sex) on brain morphology are included in the model and regressed out using an orthogonal PLS model. We looked for statistically significant correlations between brain morphology and CSF biomarkers that explain part of the volumetric variance at each region-of-interest (ROI). Furthermore, we used a clustering technique to discover a small set of CSF-related patterns describing the AD continuum. We applied this technique to the study of subjects in the whole AD continuum, from the pre-clinical asymptomatic stages all the way through to the symptomatic groups. Subsequent analyses involved splitting the course of the disease into diagnostic categories: cognitively unimpaired subjects (CU), mild cognitively impaired subjects (MCI), and subjects with dementia (AD-dementia), where all symptoms were due to AD. This work has been partially supported by the project MALEGRA TEC2016-75976-R financed by the Spanish Ministerio de Economía y Competitividad and the European Regional Development Fund (ERDF). AC was supported by the Spanish Ministerio de Educación, Cultura y Deporte FPU Research Fellowship. JG holds a Ramón y Cajal fellowship (RYC-2013-13054).

Currently, five classes of Immunotherapy (IT) agents are available for over 20 cancer types, including a powerful new class utilizing T cells genetically engineered to express a chimeric antigen receptor (CAR-T). Additional classes include bi-specific T-cell engagers (BiTEs), immune checkpoint inhibitors (ICIs), cancer vaccines, and oncolytic viruses. Despite promising antitumor activity, significant immune-related adverse events (irAE) have been reported. The most common CAR-T toxicity is cytokine release syndrome (CRS), and management typically includes supportive care and immunosuppression with corticosteroids or the IL-6 inhibitor tocilizumab. Documented CRS and tocilizumab use outside of CAR-T is rare, but recent evidence suggests that tocilizumab is emerging for management of other steroid-refractory irAE. Given the rapid evolution of this field, there remains a need to understand the utilization of IT and the pathophysiology of irAE in real-world settings. To identify cohorts of interest, a retrospective, multicenter review was conducted using Health Catalyst’s extended real-world data database, Touchstone, which includes >300 sources of data and over 70 multipayer and geographically diverse provider clients. Cohorts were selected from representative provider networks, including large and specialty academic medical centers (AMCs), integrated delivery networks, accountable care organizations, and community hospitals in the US. A total of 10 clients’ de-identified electronic medical records were searched for presence of cancer-associated diagnosis codes. The cohort was then restricted by the presence of medication order or administration of any IT-class drug, and among these, first administration of tocilizumab within 21 days. Across ten provider networks containing data for ~5.6 million cancer patients, 9,029 patients were identified: CAR-T, 116 patients (0-102); BiTEs, 112 patients (0-64); ICIs, 8,402 patients (0-4520); cancer vaccines, 182 patients (0-143); and oncolytic viruses, 217 patients (0-214). As expected, CAR-T administration was limited to approved treatment centers. Among the other classes, an average of 26% of identified patients were from the community setting. Additionally, of the 116 patients receiving CAR-T therapy, 75 patients (64.7%) were administered tocilizumab within 21 days. Evidence of tocilizumab use outside of CAR-T irAE was also identified, occurring in 21 patients (0.3%) receiving another class of IT within AMCs, and did not occur at other provider types. Together this analysis identified several real-world IT patient cohorts comprising diverse populations from a range of provider types, with corresponding access to rich patient-level clinical, molecular, and financial real-world data (RWD) elements. Immediate downstream applications will involve developing integrated methods for the real-time identification of patients who may be at risk for adverse events and standardization of toxicity management guidelines. Citation Format: Catherine Del Vecchio Fitz, Elizabeth Eldridge, Alyssa Antonopoulos, Paula Petrone, Will Caldwell, Ed Corbett, Amy Flaster, Holly Rimmasch, Adem Albayrak, Dale Sanders, Sadiqa Mahmood, Elia Stupka. Identification of multisite real-world patient cohorts to enable immunotherapy utilization and safety assessment [abstract]. In: Proceedings of the AACR Special Conference on Advancing Precision Medicine Drug Development: Incorporation of Real-World Data and Other Novel Strategies; Jan 9-12, 2020; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_1):Abstract nr 28.