A prospective cohort study of 260 patients with lymphoma after standard chemotherapy investigated dynamic changes in serum IL-6, TNF-α and β₂-microglobulin as early predictors of relapse. 78 patients (30%) relapsed, with all three biomarkers significantly higher in the relapsed group at end of treatment (T1), with even greater differences at 3 (T2) and 6 months (T3). Three months after treatment, IL-6 (adjusted OR = 1.08) and β₂-MG (adjusted OR = 1.38) were independent predictors of relapse, along with Ann Arbor stage and IPI score. β₂-MG had the strongest individual predictive value (AUC = 0.85), while the combination of IL-6 + TNF-α + β₂-MG achieved AUC = 0.91. Higher levels were associated with shorter relapse-free survival: IL-6 (HR = 1.78), TNF-α (HR = 1.52), β₂-MG (HR = 2.06). Dynamic changes in ΔIL-6 (OR = 1.21) and Δβ₂-MG (OR = 1.34) indicate early biological progression before radiological relapse.[1]