Abstract P039

Has Frontline Brentuximab Vedotin Plus AVD Altered the Historical Adverse Prognostic Impact of Stage IV Disease in Classical Hodgkin Lymphoma? A Dual-Center Real-World Experience

Background: Advanced-stage classical Hodgkin lymphoma (cHL) is traditionally associated with progressively worse outcomes with increasing stage, with stage IV disease showing inferior progression-free survival (PFS). Since 2021 strategies have evolved at our institutions according to national treatment authorization, while maintaining a PET-oriented approach: stage IIB–III patients were treated with ABVD-based regimens, while stage IV patients received frontline brentuximab vedotin plus AVD (BV-AVD). We investigated whether this therapeutic shift has altered the prognostic impact of stage on PFS.

Methods: We retrospectively analyzed consecutive patients with newly diagnosed cHL stage IIB–IV treated across two Italian centers from September 2021 onward. All patients were managed according to a PET-oriented treatment strategy. PFS was calculated from first-line treatment initiation to progression, relapse, death, or last follow-up using Kaplan–Meier estimates. Exploratory Cox proportional hazards models were performed to identify variables associated with PFS.

Results: Seventy-seven patients were included; median age at diagnosis was 37 years (IQR 27–53), and 55.8% presented with stage IV disease. B symptoms were present in 76.7%, extranodal involvement in 57.3%, and bulky disease in 49.3%. After a median follow-up of 32 months (IQR: 16-46 months), 14 PFS events were observed. Overall estimated PFS at 24 months was 79.8% (95%CI: 68.2% - 87.6%). Contrary to historical expectations, stage IV patients did not show inferior outcomes compared with stage IIB–III disease. Estimated 24-month PFS was 84.9% in stage IV and 74.0% in stage IIB–III patients (univariable Cox model, HR=0.60; 95%CI 0.21–1.72; p=0.338). Exploratory univariable Cox models identified leukocytosis ≥15×109/L (HR=4.36; 95%CI: 1.38-13.83; p=0.012) and bulky disease (HR=3.84; 95%CI: 1.06-13.97, p=0.041) as variables associated with worse PFS.

Conclusions: In this dual-center real-world PET-guided cohort, stage IV cHL did not retain its historically adverse prognostic impact and showed numerically superior PFS to stage IIB–III disease. Despite the limitations of retrospective design, sample size, and stage-based treatment allocation, these findings suggest that frontline BV-AVD may mitigate the traditional prognostic disadvantage of stage IV disease. Prospective validation is needed.