Durable 3-Year Superiority of N-AVD in Advanced Hodgkin Lymphoma

Tatyana Feldman, MD, medical oncologist specializing in lymphoma at John Theurer Cancer Center, Hackensack University Medical Center, discusses findings from long-term follow-up of the phase 3 SWOG S1826 study presented at the 2025 ASH Meeting.¹

The randomized phase 3 S1826 study evaluates the long-term efficacy and safety of nivolumab (Opidvo) combined with AVD (doxorubicin, vinblastine, and dacarbazine) compared to the former standard, brentuximab vedotin (BV; Adcetris) plus AVD, in patients with previously untreated advanced-stage (AS) classic Hodgkin lymphoma (cHL). This updated analysis provides data from a median follow-up of 3.1 years, reinforcing the durability of previous findings.

Study Design and Population

The trial enrolled 994 patients (970 eligible for analysis) aged 12 to 83 years. Participants were randomized 1:1 to receive six cycles of either N-AVD or BV-AVD. The cohort was diverse, including adolescents (24%), older adults over 60 (10%), and high-risk patients with an International Prognostic Score (IPS) of 4–7 (32%). Notably, radiation therapy was utilized in less than 1% of all cases.

Key Efficacy Findings

The 3-year data confirms that N-AVD significantly prolongs progression-free survival (PFS) compared to BV-AVD:

• Overall 3-year PFS: 91% for N-AVD vs. 82% for BV-AVD (HR 0.48).
• Adolescents (12–17y): 93% vs. 82% (HR 0.36).
• Older Adults (>60y): 82% vs. 58% (HR 0.33).
• High-Risk (IPS 4–7): 87% vs. 77% (HR 0.57).

The PFS benefit remained consistent across all subgroups, including disease stage and IPS. Event-free survival (EFS) also favored N-AVD (HR 0.56). While overall survival (OS) trends toward N-AVD (98% vs. 97%), the difference has not yet reached statistical significance.

Safety and Conclusions

N-AVD remained well-tolerated with no new safety signals. Interestingly, fewer second cancers were reported in the N-AVD arm (1.2%) compared to the BV-AVD arm (2.3%).

The study concludes that N-AVD provides durable remissions and superior outcomes across all age groups and risk profiles. These results solidify N-AVD as a preferred frontline standard of care for advanced-stage classic Hodgkin lymphoma.

In December 2025, the FDA accepted for priority review the supplemental biologics license application for nivolumab-AVD for the treatment of adult and pediatric patients 12 years and older with previously untreated stage III or IV classical Hodgkin lymphoma, with an expected target action date of April 2026.²

REFERENCES

1. Herrera A, Leblanc M, Castellino S, et al. 3-year follow-up of the S1826 study confirms improved progression-free survival with nivolumab-AVD compared to brentuximab vedotin-AVD in advanced stage classic Hodgkin lymphoma. Presented at: 67th ASH Annual Meeting; December 6–9, 2025; Abstract 151.

2. U.S. Food and Drug Administration (FDA) grants priority review to Bristol Myers Squibb's application for Opdivo (nivolumab) plus chemotherapy combination for classical Hodgkin lymphoma. News release. Bristol Myers Squibb. December 11, 2025. Accessed December 19, 2025. https://tinyurl.com/3beyhyw