Marie‐Helene Delfau‐Larue

Summary Approximately 20%–50% of patients with large B‐cell lymphoma (LBCL) experience poor outcomes. We aimed to evaluate the combined prognostic value of circulating tumour DNA (ctDNA) and total metabolic tumour volume (TMTV) in LBCL. This observational single‐centre study included 112 newly diagnosed LBCL patients, receiving R‐CHOP/R‐CHOP‐like chemotherapies. CtDNA load was calculated following next‐generation sequencing of cell‐free DNA (cfDNA) using a targeted 40‐gene lymphopanel. TMTV was measured using a fully automated artificial intelligence‐based method for lymphoma lesion segmentation. CtDNA was detected in cfDNA samples from 95 patients with a median concentration of 3.15 log haploid genome equivalents per mL. TMTV measurements were available for 102 patients. The median TMTV was 501 mL. High ctDNA load (>3.57 log hGE/mL) or high TMTV (>200 mL) were associated with shorter 1‐year PFS (44% vs. 83%, p < 0.001 and 64% vs. 97%, p = 0.002, respectively). When combined, three prognostic groups were identified. The shortest PFS was observed when both TMTV and ctDNA load were high ( p < 0.001). Even with a short follow up, combining ctDNA load with TMTV improved the risk stratification of patients with aggressive LBCL. In the near future, very high‐risk patients could benefit from CAR T‐cell therapy or bispecific antibodies as first‐line treatments.