Impact of EBV status and histology on patient outcomes with nivolumab-AVD vs BV-AVD in advanced classic Hodgkin lymphoma (S1826).

Classic Hodgkin lymphoma (cHL) associated with Epstein-Barr virus (EBV) positive status as well as nonnodular sclerosis (non-NS) histologic subtypes has demonstrated poorer outcomes compared with EBV- and NS tumors. We report a prespecified subset analysis of patients enrolled in the phase 3 SWOG S1826 trial to evaluate outcomes based on EBV status and histologic subtype in patients treated with N-AVD (nivolumab-AVD) or BV-AVD (brentuximab vedotin-AVD). In the phase 3 SWOG S1826 trial, patients with stage III to IV cHL were randomized to N-AVD or BV-AVD treatment. Of 970 eligible patients, 522 had known EBV status. N-AVD improved 3-year progression-free survival (PFS) in patients who were EBV+ (91% vs 70%; hazard ratio [HR], 0.30; P = .01) and EBV- (90% vs 84%; HR, 0.64; P = .09). Among 664 patients with slides available for histology review, 102 (15.4%) had non-NS histologic subtypes. N-AVD prolonged 3-year PFS in patients with non-NS histologic subtype (86% vs 63%; HR, 0.33; P = .006) and NS histologic subtype (93% vs 86%; HR, 0.53; P = .01). Non-NS histologic subtype was independently associated with inferior outcomes (HR, 2.54; P< .0001) after adjusting for treatment in the entire cohort. However, N-AVD treatment still had favorable PFS within this high-risk group. In addition, patients with EBV+ status or non-NS histologic subtype cHL treated with BV-AVD had significantly worse PFS (HR, 1.97; P = .03 for EBV and HR, 3.08; P< .0001 for histology). N-AVD substantially abrogated the historically poor prognosis associated with EBV+ status and non-NS histologic subtype in advanced-stage cHL. These results support N-AVD as a frontline standard of care, particularly in high-risk biologic subgroups. This trial was registered at www.clinicaltrials.gov as NCT03907488.