Prognostic Value of Lymphopenia and Total Metabolic Tumor Volume in Diffuse Large Cell Lymphoma of B Phenotype in the RT3 and REMARC trials—A LYSA retrospective analysis

Introduction: New prognostic factors have emerged such as total metabolic tumor volume (TMTV) assessed by PET-CT in large B cell lymphoma (DLBCL). Normal T, B and NK cells are also involved in antitumoral response. What is the impact of lymphopenia at the time of diagnosis on a large population? Methods: We pooled 1095 patients from 3 LYSA studies (GAINED, RT3 and REMARC) with TMTV and Lymphocytes available. Results: The three studies differ for mean age at diagnosis: GAINED patients were younger (median 48; IC: 18–61) than in RT3 (66; 20–92) and REMARC (68, 64–73). Patients with lymphocytes ≤1.0 G/L differed from patients with lymphocytes >1.0 G/L in terms of presence of B symptoms (44.5% vs. 30.0%, p < 0.001), number of extra-nodal sites involved (median of 2 vs. 1, p < 0.001), ECOG ≥ 2 (17.4% vs. 11.8%, p = 0.011), Ann Arbor stage III-IV (85.3% vs. 80.4%, p = 0.037), LDH > Upper limit (76.6% vs. 57.8%, p < 0.001), Albumin (median of 36.7 vs. 39.0 g/l, p < 0.001), IPI 3–5 (57.8% vs. 42.8%, p < 0.001), and TMTV (median of 389.3 vs. 165.3, p < 0.001). Patients with Lymphocytes ≤1.0 G/L were 39.8% and were different between the 3 studies (p = 0.008). 42.5% (n = 273 GAINED), 28.8% (n = 44 RT3) and 39.7% (n = 119 REMARC). Median TMTV was 242 cm3 overall and was different between the 3 studies (p < 0.001), 257 cm3 (GAINED), 147 (RT3) and 237 (REMARC). PFS assessment was different between RT3 and REMARC. Patients from RT3 had a higher risk of PFS (HR of 1.48 (95% CI. 1.0–2.2, p = 0.044)). No difference of OS was observed between the 3 studies (p = 0.44) An impact of TMTV was observed on PFS (p < 0.001) and OS (p < 0.001). Patients with TMTV > 220 cm3 had higher risk (HR = 1.71 (95% CI: 1.3–2.2) for PFS and HR = 2.06 (95% CI: 1.4–2.9) for OS). At a threshold of 1.0 G/L, PFS was not different (p = 0.14) but OS was different between patients with lymphocytes ≤1.0 G/L and patients >1.0 G/L (HR = 0.70 95% CI: 0.5–0.97 for patients with lymphocyte >1.0G/L, p = 0.033). No difference was observed for PFS (p = 0.98) and OS (p = 0.90) in the GAINED study. No difference was observed for PFS (p = 0.18) but OS differed between both groups (HR = 0.36 95% CI: 0.1–0.92 for patients with lymphocytes >1.0 G/L, p = 0.036) in the RT3 study. PFS and OS differed in the REMARC study (p = 0.021 and p = 0.0074, respectively). Patients with lymphocytes >1.0 G/L had lower risk of PFS (HR = 0.59 95% CI: 0.4–0.93) and OS (HR = 0.49 95% CI: 0.3–0.8). Keywords: Diagnostic and Prognostic Biomarkers, PET-CT No conflicts of interests pertinent to the abstract.