Lymphoma Outcomes SPORE - Across lymphoma subtypes, African American (AA) and Hispanic patients experience marked differences in age of onset, disease presentation, treatment, and survival. Biologic and patient-level factors contribute to inferior outcomes for specific patients but remain poorly understood. These groups are understudied in clinicopathologic cohorts examining lymphoma pathogenesis and therapeutic targets, in lymphoma clinical trials and are also more likely to receive care at under-resourced community practices, where lack of onsite hematopathology can lead to delayed or inaccurate lymphoma diagnosis. We have developed unparalleled resources to examine and address the multilevel factors influencing lymphoma outcomes. We established the multicenter Lymphoma Epidemiology of Outcomes Cohort Study, prospectively enrolling >13,000 lymphoma patients with banked tumor tissue, germline DNA, and linked pathology, demographic, treatment, and survival data on all patients. We performed the first large-scale genomic analyses of the most common lymphoma subtype, diffuse large B-cell lymphoma (DLBCL), from patients with African ancestry and identified that in addition to patient-level factors such as inferior access to care, AA patients with DLBCL have specific tumor mutations such as SETD2 and microenvironment phenotypes that may impact clinical outcomes. By developing murine and human SETD2 mutation models, we found these lymphomas feature genomic instability, a senescence-associated secretory phenotype, and an inflammatory microenvironment that can be effectively therapeutically targeted using SETD2 inhibitors available for use in humans in a trial. We hypothesize that these and other novel patient subsets can be readily diagnosed in the community from simple H&E slides, through deconvolution of complex tissue architecture. We contend that these data are clinically actionable through evidence-based community interventions, so that precision therapy for patients with lymphoma can be successfully implemented in clinical trials and in routine care, guided by their relevant predictive biomarkers. The overarching goal of this SPORE is to overcome gaps in knowledge, survival, and access to cancer care through a comprehensive bench-to-bedside-to-community approach that interrogates the relationships between ancestry, lymphoma biology, and patient outcomes; evaluates strategies to improve clinical trial participation and survival rates; and develops population-specific models, accessible diagnostic tools, targeted therapies, and active engagement with community oncology practices to improve care and outcomes for all patients.
