A Risk Score Incorporating Low Pass Whole Genome Sequencing of Cell Free DNA from Patients Receiving CD19 CAR T-Cell Therapy for Large B-Cell Lymphoma

Patients (pts) with relapsed or refractory large B-cell lymphomas (rrLBCL) can achieve long-term remission after CD19 chimeric antigen receptor T-cell therapy (CART), but more than half of recipients will experience treatment failure. High pretreatment tumor burden by elevated LDH, metabolic tumor volume, or circulating tumor DNA (ctDNA) levels by clonotype sequencing are associated with inferior outcomes. Low pass whole genome sequencing (lpWGS) is a highly simplified assay capable of identifying copy number alterations (CNA) from cell free DNA (cfDNA) in blood and requires less time, cost, and sample volume to perform vs. other cfDNA sequencing methods; it may be an efficient and precise proxy for tumor burden to identify pts at high risk of progression after CART. Here, we performed lpWGS on pretreatment plasma samples from pts who received CART for rrLBCL and incorporated it into a prognostic risk model.EGA study EGAS00001006308