NGS-determined molecular markers and disease burden metrics from ctDNA correlate with PFS in previously untreated DLBCL.

Personalized risk stratification and treatment may help improve outcomes among patients with diffuse large B-cell lymphoma (DLBCL). We developed a next-generation sequencing (NGS)-based method to assess a range of potential prognostic indicators, and evaluated it using pretreatment plasma samples from 310 patients with previously untreated DLBCL from the GOYA trial (NCT01287741). Variant calls and DLBCL subtyping with the plasma-based method were concordant with corresponding tissue-based methods. Patients with a tumor burden greater than the median ( = .003) and non-germinal center B-cell-like (non-GCB) DLBCL ( = .049) had worse progression-free survival than patients with a tumor burden less than the median or GCB DLBCL. Multi-factor assessment combining orthogonal features from a single pretreatment plasma sample has promise as a prognostic indicator in this setting ( = .085). This minimally invasive plasma-based NGS assay could enable comprehensive prognostic assessment of patients in a clinical setting, with greater accessibility than current methods.