Additional Study Information: This research study is studying the phased variant enrichment and detection sequencing (PhasED-seq) circulating tumor DNA (ctDNA) assay in diffuse large B-cell lymphoma (DLBCL). The PhasED-seq assay is a blood test to measure tiny fragments of material released into the blood by lymphoma called circulating tumor DNA. The purpose of this study is to 1) determine whether it is feasible to measure ctDNA in real-time during standard treatment for newly diagnosed DLBCL, and 2) evaluate the outcomes of participants with undetectable ctDNA in the middle of treatment who receive a shortened course of chemotherapy. The PhasED-seq assay has not yet been approved by the Food and Drug Administration (FDA).