FDA Approves Nivolumab Plus AVD for Untreated Classical Hodgkin Lymphoma

The FDA has approved nivolumab (Opdivo) in combination with doxorubicin, vinblastine, and dacarbazine (AVD) for the treatment of adult and pediatric patients 12 years and older with previously untreated stage III or IV classical Hodgkin lymphoma.¹

The FDA has also granted traditional approval to nivolumab for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma following autologous hematopoietic stem cell transplantation (HSCT) and brentuximab vedotin (Adcetris), or following at least 3 prior lines of systemic therapy, including autologous HSCT.

The approval of nivolumab plus AVD was supported by data from the randomized, open-label, multicenter phase 3 CA209-8UT/SWOG 1826 study (NCT03907488), which evaluated nivolumab plus AVD vs brentuximab vedotin plus AVD in patients 12 years and older with previously untreated stage III or IV classical Hodgkin lymphoma. At a median follow-up of 13.7 months, the median progression-free survival (PFS) was not reached in either arm, with PFS outcomes favoring the nivolumab arm (HR, 0.42; 95% CI, 0.27-0.67; P < .0001).

Furthermore, at a median follow-up of 36.7 months, 1.8% of patients in the nivolumab arm had died; 3.4% of those in the brentuximab vedotin arm had died.

What was the design of Study CA209-8UT?

This trial randomly assigned 994 patients 1:1 to receive 6 cycles of either nivolumab plus AVD or brentuximab vedotin plus AVD.

PFS per investigator review served as the primary end point. Secondary end points included event-free survival, overall survival, end-of-treatment complete metabolic response rate, and patient-reported outcomes.²

What additional efficacy findings have been seen with nivolumab plus AVD in Study CA209-8UT?

Data from the 3-year follow-up of CA209-8UT presented at the 2025 ASH Annual Meeting showed that at a median follow-up of 3.1 years (range, 0-5.5), the estimated 3-year PFS rate was 91% (95% CI, 88%-93%) in the nivolumab arm (n = 487) vs 82% (95% CI, 78%-85%) in the brentuximab vedotin arm (n = 483; HR, 0.48; 95% CI, 0.34-0.69; P < .0001).

This PFS benefit with nivolumab plus AVD was consistent across prespecified patient subgroups at the 3-year mark, regardless of International Prognostic Score, disease stage, or the presence of A vs B symptoms.

Specifically, in patients 18 to 60 years of age, the estimated 3-year PFS rates in these respective arms were 91% (95% CI, 87%-94%; n = 321) and 85% (95% CI, 81%-94%; n = 318; HR, 0.62; 95% CI, 0.39-0.98; P < .015). In adolescent patients, these respective rates were 93% (95% CI, 87%-96%; n = 118) and 82% (95% CI, 73%-88%; n = 118; HR, 0.36; 95% CI, 0.17-0.79; P < .004). In older adult patients, these respective rates were 82% (95% CI, 68%-91%; n = 48) and 58% (95% CI, 42%-71%; n = 47; HR, 0.34; 95% CI, 0.15-0.77; P < .003).

What safety findings from Study CA209-8UT are important to note?

Among patients who received nivolumab plus AVD, the rate of serious adverse effects (AEs) was 39%.¹ Additionally, any-grade and grade 3/4 immune-mediated AEs were reported in 9% and 2.7% of patients, respectively.

The recommended dosing for the regimen is nivolumab at 240 mg for adult and pediatric patients who weigh at least 40 kg, or 3 mg/kg for pediatric patients who weigh less than 40 kg; the agent is administered IV in combination with AVD on days 1 and 15 of each 28-day cycle for a maximum of 6 cycles. Notably, primary granulocyte colony–stimulating factor prophylaxis is recommended to begin in cycle 1.

References

1. FDA approves nivolumab with chemotherapy for previously untreated Hodgkin lymphoma. FDA. March 20, 2026. Accessed March 20, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-nivolumab-chemotherapy-previously-untreated-hodgkin-lymphoma
2. 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. Blood. 2025;146(suppl 1):151. doi:10.1182/blood-2025-151