C035 | LINKING TUMOR BURDEN AND IMMUNE PROFILES IN HODGKIN LYMPHOMA: PROGNOSTIC VALUE OF TMTV AND CD19⁺ B CELLS

Tumor burden, systemic inflammation, and immune competence are central to Hodgkin lymphoma (HL) biology. While TMTV is prognostic, its relationship with immune parameters and their contribution to disease behavior remains to be explored. We retrospectively analyzed 92 newly diagnosed classical HL patients (2016–2024) who underwent baseline [18F]FDG-PET/CT and pre-treatment blood tests: mean age 38 y; 54% female, 43% advanced stage. TMTV was calculated using semi-automated segmentation (syngo.via, Siemens; PERCIST threshold). Blood parameters included CRP, ESR, fibrinogen, monocytes, neutrophils, NK cells, and lymphocyte subsets(CD4⁺, CD8⁺,CD19⁺). Principal component analysis (PCA) was used to identify immuno-metabolic patterns. PCA identified four components: cytokine-driven inflammation (Component 1: CRP=+0.856, ESR=+0.835), adaptive immunity inversely related to TMTV (Component 2: CD4+=+0.794, CD8+=+0.612,CD19+=+0.607, TMTV=-0.530), TMTV linked to monocytes/neutrophils (Component 3: TMTV=+0.570, monocytes=+0.526, neutrophils=+0.356), and NK cells (Component 4: CD56+CD16+=+0.905). TMTV inversely correlated with adaptive immunity, suggesting tumor-associated immunosuppression. In multivariate Cox analysis including these variables, only TMTV was independently associated with worse prognosis (HR 1.007; 95% CI 1.002-1.011; p=0.002). Pts with above average TMTV (≥129.45mL, n=24) had significantly lower 24-month PFS (66.7% vs 85.5%, p=0.027). Given the strong inverse relationship between TMTV and adaptive immunity, we explored the prognostic role of lymphocyte subsets within the high-TMTV group. Only CD19⁺ counts<45.5 cells/mm³ (median value in high-TMTV) predicted worse PFS(46.2% vs 90.9%; log-rank p=0.05). That CD19⁺ counts in PB were markedly lower in patients with high vs low TMTV ([45.5 vs 110] cells/mm³, p<0.00001) and only 8% of low-TMTV patients showed low CD19⁺ counts, and that high-TMTV pts who relapsed had lower baseline CD19+ counts ([33 vs 61.5] cells/mm3; p=0.03) suggests that TMTV impacts CD19⁺ counts and that these B-cells may play a protective role in HL. In patients with low TMTV (n=62), CRP>14.7 mg/L (median in low TMTV) predicted reduced 24-month PFS (72.4% vs 100%, log-rank p=0.001). In conclusion, TMTV captures not only disease burden but also its systemic immunosuppressive imprint. Its prognostic value, together with that of inflammatory and CD19⁺ counts, supports their integration into risk stratification models in HL.