Abstract P011

Interim analysis of the A-AVD PET2 adapted in patients with stage IV classical Hodgkin lymphoma. The AVATAR program

Background: In the ECHELON-1 trial brentuximab-AVD (A-AVD) improved the progression-free survival (PFS) and overall survival (OS) stage IV classical Hodgkin lymphoma (cHL) compared to ABVD. This trial, alongside other real-life studies confirmed the predictive role of the 18FDG PET-CT scan after the two courses of A-AVD (PET2), with PET2 positivity (PET2+) associated with a higher risk of relapse. Recently in the COBRA trial almost 40% of the patients with a positive PET after 1 cycle of A-AVD escalated to BrECADD for 6 cycles with a 2-yr PFS of 89%. We hypothesized that escalation to BrECADD in PET2+ cases would reduce the number of patients requiring treatment intensification while improving their outcomes.

Methods: Patients with stage IV cHL aged 18–60 years were treated with A-AVD for 2 cycles according to Italian regulatory agency. Patients with a negative PET2 scan (Deauville score 1–3) continued A-AVD until cycle 6, whereas those with a positive PET2 scan (DS 4–5) received 4 cycles of BrECADD. Consolidative radiotherapy (cRT) was provided in case of focal residual disease at the end of treatment (EoT).

Results: Fifty patients with stage IV cHL have been enrolled since 2021, 46% were male, median age was 31 years (IQR 25-43), 62% had B symptoms, 38% an IPS >3, 20% a bulky mass and 6% were HIV positive. Regarding histology, 70% had nodular sclerosis subtype, 4% mixed cellularity, 2% lymphocyte-rich, 2% lymphocyte depletion, 22% NOS. Only 10% of cases were PET2+ (6% DS 4, 4% DS 5). Among 90% PET2 negative cases, only 2 patients had a positive EoT PET, 1 with localized diseases received cRT achieving a complete remission. Among the 5 PET2+ patients, 1 patient with localized EoT PET positivity received cRT. Only 1 patient in both subgroups relapsed, after 2 and 9 months, respectively. After a median follow-up of 24 months the 2-yr PFS and OS were 92.2% and 97.6%. Only 1 HIV+ PET2 negative patient died of infection at cycle 5. As expected, cytopenias, blood transfusion and fatigue were more common with BrECADD, while the rate of peripheral neuropathy (PN) was higher patients who received 6 cycles of A-AVD. Thus since February 2026, to reduce the incidence of PN, PET2-negative patients are receiving A-AD (i.e w/o vinblastine).

Conclusions: In our ongoing program, we confirmed the low rate of PET2+ after of A-AVD and provide initial results that 4 cycles of BrECADD can successfully rescue most PET2+ patients.