Nivolumab (PD-1) + AVD lifts 3-year PFS in EBV+ and non–nodular sclerosis advanced cHL vs BV-AVD

Nivolumab-AVD (N-AVD) combines PD-1 blockade (nivolumab) with doxorubicin/vinblastine/dacarbazine chemotherapy, and in the Phase 3 SWOG S1826 frontline trial in stage III–IV classic Hodgkin lymphoma (NCT03907488), this prespecified subset analysis found benefit across historically higher-risk biology. Among patients with known EBV status (n=522), 3-year PFS favored N-AVD over brentuximab vedotin-AVD (BV-AVD; CD30-directed ADC + AVD) in EBV-positive disease (91% vs 70%; HR 0.30; p=0.01) and also in EBV-negative disease (90% vs 84%; HR 0.64; p=0.09). In the centrally reviewed histology cohort (n=664; non-NS n=102 [15.4%]), N-AVD improved 3-year PFS in non-nodular sclerosis subtypes (86% vs 63%; HR 0.33; p=0.006) and nodular sclerosis (93% vs 86%; HR 0.53; p=0.01); non-NS histology remained independently adverse overall (HR 2.54; p<0.0001), but the excess risk looked meaningfully “flattened” on N-AVD—contrasting with BV-AVD, where EBV positivity (HR 1.97; p=0.03) and non-NS histology (HR 3.08; p<0.0001) tracked with substantially worse PFS. As a practical benchmark, BV-AVD itself was an established frontline option based on ECHELON-1’s long-term PFS advantage vs ABVD (e.g., ~85% 5-year PFS in PET2-negative patients on BV-AVD), so seeing BV-AVD’s 3-year PFS fall to 63–70% in these high-risk subsets underscores how much biology can matter—and how large the relative lift with PD-1 + AVD appears here.