P024 | COMBINATION OF BASELINE CA125 LEVELS AND EOT FDG-PET DYNAMICALLY STRATIFIES FAILURE RISK IN PATIENTS WITH PRIMARY MEDIASTINAL B-CELL LYMPHOMA TREATED WITH DA-EPOCH-R: A REAL-LIFE RETROSPECTIVE ANALYSIS.

Introduction: Modern immune-chemotherapy may cure nearly 85% of patients (pts) with Primary Mediastinal B-cell Lymphoma (PMBCL) but controversies exist regarding optimal frontline regimen and prognostic factors to guide treatment selection. This study explored interactions among prognostic and predictive factors in pts receiving DA-EPOCH-R in a real-life setting. Methods: We retrospectively analyzed 66 adult patients (Fig 1) treated with DA-EPOCH-R from 2008 to 2024 at the INT Fondazione G. Pascale (Italy) to identify clinical and biological factors influencing outcomes to this frontline treatment. Event-free survival (EFS) was calculated from treatment initiation until relapse, refractoriness, treatment diversion, or death from any cause. Overall survival (OS) was calculated from treatment initiation until death from any cause. Results: Median observation time was 52 months (range 5-176). Complete response rate (CRr; Lugano criteria) was 81.8% (54/66) with 13.6% (9/66) of primary refractory pts (progressing/refractory during treatment or relapsed within 12 months). Five patients (7.6%) received less than 6 cycles of therapy due to G3-4 toxicities. Five-year EFS was 82.4%, with a 5-year OS of 96.6%. Higher CA125 levels at diagnosis (threshold >54.5 U/mL by ROC analysis) was the only variable associated with a worse CRr (HR 9.50, p=.041). At diagnosis, R-IPI (P=.026) and CA125 levels (P=.041) impacted EFS in univariate analysis, but only CA125 levels (>54.5 U/mL) were independently associated with a worse EFS in multivariable analysis (HR 8.45, p=.049) (Fig 1). Variables associated with elevated CA125 level were younger age at diagnosis (median 40.5 vs 32 years, p=.039), ECOG >1 (OR 7.20, p=.022), presence of pleural (OR 6.67, p=.004) or pericardial effusion (OR 5.10, p=.017), and LDH >2x ULN (OR 6.19, p=.024). Receiving <6 cycles of therapy (p=.026) and a positive FDG-PET scan (DS 4-5) at the end of treatment (EOT, P<.001) influenced EFS, but only positive EOT FDG-PET scan remained significant in multivariable model (HR 37.93, p=.002). Only age at diagnosis as continuous variable associated with worse OS (HR 1.13, p=.044). Conclusions: Despite the limitations, our study showed CRr and EFS with DA-EPOCH-R are largely unaffected by most known prognostic factors at diagnosis, except for elevated levels of CA125 (>54.5 U/mL). Combination of baseline CA125 and EOT FDG-PET may concur to dynamically stratify failure risk in PMBCL pts receiving DA-EPOCH-R.