Trněný M, et al. - Given a poor prognosis for patients (pts) with diffuse large B-cell lymphoma (DLBCL) refractory to treatment with standard frontline rituximab (R)-based immunochemotherapy, and no clinical tools available to identify these pts, researchers conducted this exploratory analysis examining primary refractoriness in previously untreated pts with DLBCL from the phase 3 GOYA trial. Either obinutuzumab (G)- or R-CHOP was administered to the pts (G 1000 mg cycle [C]1 day [D]1, 8 and 15, and C2–8 D1; R 375 mg/m² C1–8 D1; CHOP 6 or 8 cycles every 21 days). Those with no metabolic response or progressive metabolic disease (PMD) at end of treatment (EOT) by Independent Review Committee using Lugano PET criteria, or progression (PD)/death due to PD before EOT by investigator were defined as primary refractory pts. GOYA comprised 1418 pts; of these 113 (8.0%) were identified as primary refractory (median age 61 years; 54% male). Outcomes revealed that in previously untreated pts with DLBCL, the only independent prognostic factor for primary refractoriness was tumor metabolic total volume (TMTV), implying the association of responsiveness to immunochemotherapy with tumor burden. As a prognostic factor, TMTV may help to identify high-risk pts who may benefit from an alternative therapeutic strategy.