FDA Approves Nivolumab Plus AVD for Classical Hodgkin Lymphoma

The FDA has approved the combination of nivolumab (Opdivo) with doxorubicin, vinblastine, and dacarbazine (AVD) for adult and pediatric patients with previously untreated stage III or IV classical Hodgkin lymphoma (cHL).¹

In December 2025, the FDA accepted and granted priority review to the supplemental biologics application of nivolumab plus AVD (N-AVD).²

This acceptance followed results from the phase 3 SWOG S1826/CA2098UT (NCT03907488) study, a randomized, open-label, multicenter trial sponsored by the National Cancer Institute through the National Clinical Trials Network (NCTN).³ The trial evaluated the safety and efficacy of N-AVD vs brentuximab vedotin (Adcetris) combined with AVD (BV-AVD) in newly diagnosed patients with cHL.

Findings from the interim analysis demonstrated that N-AVD had a superior progression-free survival (PFS) vs BV-AVD with a median follow-up of 12.1 months (HR, 0.48; 99% CI, 0.27-0.87). The estimated 1-year PFS rates were 94% for patients treated with N-AVD vs 86% for patients treated with BV-AVD. The 2-year PFS reached 92% in the N-AVD arm vs 83% in the BV-AVD arm (HR, 0.45; 95% CI, 0.30-0.65).

The N-AVD regimen offers a distinct toxicity profile, notably mitigating the neurologic risks associated with brentuximab vedotin. Sensory peripheral neuropathy (any grade) was significantly lower in the N-AVD arm (28.1% vs 54.2%). Grade 3 adverse events (AEs) were numerically higher in the N-AVD arm (48.4% vs 30.5%), though rates of febrile neutropenia remained comparable. Fewer deaths attributable to AEs occurred in the N-AVD arm. The trial also observed a low rate of consolidating radiation therapy use across both arms, suggesting effective disease control without the need for additional local intervention.

Nivolumab is already approved for use in patients with cHL that has relapsed or progressed after autologous hematopoietic stem cell transplantation and brentuximab vedotin.

While doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) has long been the frontline standard, its utility is limited by bleomycin-induced pulmonary toxicity. While BV-AVD improved PFS over ABVD, it increased rates of neutropenia and peripheral neuropathy.

The SWOG S1826 trial—the largest NCTN advanced-stage cHL study to date—integrated adult and pediatric patients. The results suggest that N-AVD may establish a new frontline standard, particularly for pediatric and young adult patients where minimizing long-term toxicities such as secondary malignancies and cardiopulmonary damage is critical.

REFERENCES

1. FDA approves nivolumab with chemotherapy for previously untreated Hodgkin lymphoma. News release. US FDA. March 20, 2026. Accessed March 20, 2026. https://tinyurl.com/3hr3f6am

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. Published December 11, 2025. Accessed January 26, 2026. https://tinyurl.com/2s473e5x

3.Immunotherapy (nivolumab or brentuximab vedotin) plus combination chemotherapy in treating patients with newly diagnosed stage III-IV classic Hodgkin lymphoma. ClinicalTrials.gov. Updated December 4, 2025. Accessed January 26, 2026. https://clinicaltrials.gov/study/NCT03907488