Classic Hodgkin lymphoma (cHL) associated with Epstein-Barr virus (EBV) positivity as well as non-nodular sclerosis (non-NS) histologic subtypes have demonstrated poorer outcomes compared to EBV-negative and nodular sclerosis cases. We report a prespecified subset analysis of patients enrolled in the phase III SWOG S1826 trial to evaluate outcomes based on EBV status and histologic subtype in patients treated with nivolumab-AVD (N-AVD) or brentuximab vedotin (BV)-AVD. In the phase III SWOG S1826 trial, patients with stage III-IV cHL were randomized to N-AVD or BV-AVD. Of 970 eligible patients, 522 had known EBV status. N-AVD improved 3-year progression-free survival (PFS) in EBV-positive (91% v 70%; HR, 0.30; P = 0.01) and EBV-negative patients (90% v 84%; HR, 0.64; P = 0.09). Among 664 patients with slides available for histology review, 102 (15.4%) had non-NS subtypes. N-AVD prolonged 3-year PFS in patients with non-NS (86% v 63%; HR, 0.33; P = 0.006) and NS histologic subtype (93% v 86%; HR, 0.53; P = 0.01). Non-NS histology independently was associated with inferior outcomes (HR, 2.54; P 0.0001) 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 positivity or non-NS histology cHL treated with BV-AVD had significantly worse PFS (HR, 1.97; P = 0.03 for EBV; and HR, 3.08; P 0.0001 for histology). N-AVD substantially abrogated the historically poor prognosis associated with EBV positivity and non-NS histology in advanced-stage cHL. These results support N-AVD as frontline standard of care, particularly in high-risk biologic subgroups. (NCT03907488)
Ahmed et al. (Wed,) studied this question.