Brentuximab vedotin (CD30 ADC) + AVEPC lifts PFS in pediatric stage IV cHL—except bone marrow-only disease

In COG AHOD1331 (NCT02166463), 2–21-year-olds with high-risk classic Hodgkin lymphoma and centrally PET-CT–confirmed stage IV disease (n=340; median age 15) were randomized to 5 cycles of ABVE-PC (bleomycin-containing pediatric SOC multi-agent chemo; n=173) vs brentuximab vedotin + AVEPC (Bv-AVEPC; CD30-directed antibody–drug conjugate replacing bleomycin; n=167). Four-year PFS varied by extranodal pattern (lung-only 88.6% vs bone marrow-only 71.9%), and across all stage IV patients Bv-AVEPC improved PFS vs ABVE-PC (HR 0.53, 90% CI 0.33–0.85); benefit was seen in lung-only and bone-only subgroups, but not in bone marrow-only involvement. Versus the broader AHOD1331 benchmark where ABVE-PC delivered ~82.5% 3-year PFS (with response-adapted RT) and Bv-AVEPC ~92.5% 3-year PFS, these data suggest marrow involvement is a biologically distinct “non-BV-rescued” risk group despite the regimen upgrade.