Key Points

  • Early identification of ultra-risk DLBCL patients is needed to aid stratification to alternative treatment approaches

  • High baseline TMTV (±ECOG) was a strong prognosticator of inferior PFS and OS in REMARC patients post-R-CHOP, irrespective of maintenance

Early identification of ultra-risk diffuse large B-cell lymphoma (DLBCL) patients is needed to aid stratification to innovative treatment. Previous studies suggested high baseline total metabolic tumor volume (TMTV) negatively impacts survival of DLBCL patients. We analyzed the prognostic impact of TMTV and prognostic indices in DLBCL patients, aged 60 to 80 years, from the phase III REMARC study that randomized responding patients to RCHOP into maintenance lenalidomide or placebo. TMTV was computed on baseline PET/CT using the 41% SUVmax method; optimal TMTV cut-off for progression-free (PFS) and overall survival (OS) was determined and confirmed by a training validation method. There were 301/650 evaluable patients (n=155 lenalidomide; n=146 placebo), including 192 patients classified as GCB/non-GCB and MYC/BCL2 expressor. Median baseline TMTV was 238 cm3 (IQR: 78-523); optimal TMTV cut-off was 220 cm3. Patients with high TMTV >220 cm3 (vs low ≤220 cm3) showed worse/higher ECOG PS ≥2, stage III-IV disease, >1 extra-nodal sites, elevated LDH, IPI 3-5, and age-adjusted IPI 2-3. High vs low TMTV significantly impacted PFS (HR=2.3; P = .0002) and OS (HR=3.3; P = .0001), independent of maintenance treatment. Although the GCB/non-GCB profile and MYC expression did not correlate with TMTV/survival, BCL2 >70% impacted PFS and could be stratified by TMTV. Multivariate analysis identified baseline TMTV and ECOG PS as independently associated with PFS and OS. Even in responding patients after R-CHOP, high baseline TMTV was a strong prognosticator of inferior PFS and OS. Moreover, TMTV combined with ECOG PS may identify an ultra-risk DLBCL population.

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