Abstract P030

Outcome and Prognostic Value of PET-2 in Stage IV Classical Hodgkin Lymphoma Treated with Frontline Brentuximab Vedotin Plus AVD: A Real-World Multinational GELTAMO-GATLA Study

Background: Real-world evidence of the benefit of Bv AVD vs. ABVD in stage IV cHL remains limited, and the prognostic value of interim PET (PET-2) is not clearly defined. Aims: Evaluate metabolic complete remission (mCR) rate, 2-year EFS, OS, toxicity and the prognostic value of PET-2 in stage IV cHL pts treated with frontline Bv-AVD in routine clinical practice within a GELTAMO and GATLA collaboration.

Methods: Retrospective multicentre cohort of stage IV cHL patients (≥16 years) treated with frontline Bv-AVD (2/2019–3/2025) at 30 centres in Spain and Argentina. PET-2 (after >= 2 cycles) mCR was DS1–3. EFS/OS calculated with Kaplan-Meier. EFS/OS predictors were assessed by uni/multivariable Cox models including age (<60 vs >= 60), IPS (1-3 vs 4-7), B symptoms, bulky (Bx) disease, PET-2 status, and ≥2 extranodal (EN) sites.

Results: 110 pts were included. Median age was 40.4 yrs (range 27.8–53.5); 80.6% ECOG 0–1, 69.1% B symptoms and 53.6% ≥2 EN sites. Bx disease in 28.2%; 38.2% IPS ≥4. Median of Bv doses was 12. PET-2 was done in 102/110 pts (92.7%) achieving 79.2% mCR. EOT PET was done in 98/110 (89.1%), 88.8% mCR rate. Consolidative RT was delivered in 4.7% pts. At a median follow-up of 28.3 m for EFS and 34 m for OS, 2-year EFS was 81.9 % [95%CI 74.6%-89.9%] and 2-year OS was 95.9% [CI95% 92%-100%]. mCR at PET-2 was associated with improved EFS (83.0% vs. 57.4%; p= 0.002) but not OS. IPS ≥4 and >=2 EN sites involvement were associated with shorter OS (85.5% vs. 98.2%, p=0.05 and 88.6% vs. 100%, p= 0.04 respectively). In multivariable analysis, PET-2 positivity remained independently associated with shorter EFS (HR 3.52; p=0.007), without significant impact on OS. 48% pts developed neutropenia (>= G3 35%) with a median of 1 cycle; 14% >= G3 febrile neutropenia. Peripheral neuropathy developed in 34% of the pts, mostly G1-2 (27%).

Conclusions: This large binational real-world study, restricted to pts with stage IV cHL, demonstrates that frontline Bv-AVD achieves favorable outcomes, with 2-year EFS and OS rates of 81.9% and 95.9%, respectively, consistent with ECHELON-1. To our knowledge, it represents the largest real-world series in stage IV pts and the first to show that PET-2 positivity independently predicts inferior EFS with Bv-AVD, although the implications for treatment adaptation require prospective validation. This collaborative GELTAMO–GATLA analysis provides a relevant benchmark for future PET-adapted strategies in this high-risk population.