S1826
A Phase III, Randomized Study of Nivolumab (Opdivo) Plus AVD or Brentuximab Vedotin (Adcetris) Plus AVD in Patients (Age >/= 12 Years) With Newly Diagnosed Advanced Stage Classical Hodgkin Lymphoma
Phase 3N = 994NCT03907488
- Population
- Previously untreated stage III or IV classic Hodgkin lymphoma, age 12 years or older.
- Design
- Multicentre, open-label, randomised phase 3 trial of nivolumab plus doxorubicin, vinblastine and dacarbazine (N+AVD) versus brentuximab vedotin plus AVD (BV+AVD); patients could receive radiation therapy to residual metabolically active lesions. Primary endpoint: progression-free survival, from randomisation to first observed progressive disease or death from any cause. 994 patients were randomised and 970 were included in the intention-to-treat efficacy population.
- Primary endpoint
- PFS
- Arms
- N+AVD (experimental): Nivolumab plus doxorubicin, vinblastine and dacarbazine
- BV+AVD (control): Brentuximab vedotin plus doxorubicin, vinblastine and dacarbazine
- People
- Herrera AF, SWOG
PFSHR 0.48PFSHR 0.45 (95% CI 0.30–0.65)Δ 24-month PFS+9 pointsPFSHR 0.24 (95% CI 0.09–0.63)Δ 24-month PFS+25 pointsOSHR 0.16 (95% CI 0.03–0.75)
Show the numbers
| Endpoint | Analysis | N+AVD | BV+AVD | Effect |
|---|---|---|---|---|
| PFSModified ITT: 970 eligible patients of 994 randomised (labelled intention-to-treat in the abstract)Time from randomisation to the first observation of progressive disease or death from any cause; response and progression assessed by investigators (Lugano 2014 criteria), per the full text. | interimmedian follow-up 12.1 monthsHerrera 2024 | — | — | HR 0.48P=0.001Second planned interim analysis; the efficacy threshold was crossed. The interval published for this analysis is a 99% CI, 0.27 to 0.87; P is two-sided. |
| PFSModified ITT: 970 eligible patients of 994 randomised (labelled intention-to-treat in the abstract)Time from randomisation to the first observation of progressive disease or death from any cause; response and progression assessed by investigators (Lugano 2014 criteria), per the full text. | long term-updatemedian follow-up 2.1 yearsHerrera 2024 | 92% at 2 y (89–94%) | 83% at 2 y (79–86%) | HR 0.45 (95% CI 0.30–0.65)Analysis repeated with longer follow-up (range 0 to 4.2 years) because of the short follow-up at the interim analysis; no P value is given in the abstract for this analysis. |
| PFSAge 60 years and older, eligible patients (99 of 103 enrolled; 50 on N-AVD, 49 on BV-AVD) | exploratorymedian follow-up 2.1 yearsRutherford 2025 | 89% at 2 y | 64% at 2 y | HR 0.24 (95% CI 0.09–0.63)P=0.001Planned subset analysis in older patients (age 60 years and older), labelled exploratory here because the subset was not the basis of the primary comparison; P is the 1-sided stratified log-rank P value. No interval estimates are given for the 2-year rates in the abstract. |
| OSAge 60 years and older, eligible patients (99 of 103 enrolled; 50 on N-AVD, 49 on BV-AVD) | exploratorymedian follow-up 2.1 yearsRutherford 2025 | 96% at 2 y | 85% at 2 y | HR 0.16 (95% CI 0.03–0.75)P=0.005Planned subset analysis in older patients (age 60 years and older), labelled exploratory here; P is the 1-sided stratified log-rank P value. Nonrelapse mortality was reported as 16% with BV-AVD and 6% with N-AVD. |
| PFSAdolescents aged 12 to 17 years (240 of 994 enrolled) | exploratoryCastellino 2026 | 93% at 3 y (87–96%) | 82% at 3 y (73–88%) | HR 0.37 (95% CI 0.17–0.80)Planned subset analysis in the adolescent cohort (median follow-up 3.1 years, range 0.2 to 5.5, per the full text), labelled exploratory here. The authors report that no progression events occurred among the patients who discontinued part or all of N-AVD early (12 patients). |
| Endpoint | Analysis | N+AVD | BV+AVD | Effect |
|---|---|---|---|---|
| PFSModified ITT: 970 eligible patients of 994 randomised (labelled intention-to-treat in the abstract)Time from randomisation to the first observation of progressive disease or death from any cause; response and progression assessed by investigators (Lugano 2014 criteria), per the full text. | interimmedian follow-up 12.1 monthsHerrera 2024 | — | — | HR 0.48P=0.001Second planned interim analysis; the efficacy threshold was crossed. The interval published for this analysis is a 99% CI, 0.27 to 0.87; P is two-sided. |
| PFSModified ITT: 970 eligible patients of 994 randomised (labelled intention-to-treat in the abstract)Time from randomisation to the first observation of progressive disease or death from any cause; response and progression assessed by investigators (Lugano 2014 criteria), per the full text. | long term-updatemedian follow-up 2.1 yearsHerrera 2024 | 92% at 2 y (89–94%) | 83% at 2 y (79–86%) | HR 0.45 (95% CI 0.30–0.65)Analysis repeated with longer follow-up (range 0 to 4.2 years) because of the short follow-up at the interim analysis; no P value is given in the abstract for this analysis. |
| PFSAge 60 years and older, eligible patients (99 of 103 enrolled; 50 on N-AVD, 49 on BV-AVD) | exploratorymedian follow-up 2.1 yearsRutherford 2025 | 89% at 2 y | 64% at 2 y | HR 0.24 (95% CI 0.09–0.63)P=0.001Planned subset analysis in older patients (age 60 years and older), labelled exploratory here because the subset was not the basis of the primary comparison; P is the 1-sided stratified log-rank P value. No interval estimates are given for the 2-year rates in the abstract. |
| OSAge 60 years and older, eligible patients (99 of 103 enrolled; 50 on N-AVD, 49 on BV-AVD) | exploratorymedian follow-up 2.1 yearsRutherford 2025 | 96% at 2 y | 85% at 2 y | HR 0.16 (95% CI 0.03–0.75)P=0.005Planned subset analysis in older patients (age 60 years and older), labelled exploratory here; P is the 1-sided stratified log-rank P value. Nonrelapse mortality was reported as 16% with BV-AVD and 6% with N-AVD. |
| PFSAdolescents aged 12 to 17 years (240 of 994 enrolled) | exploratoryCastellino 2026 | 93% at 3 y (87–96%) | 82% at 3 y (73–88%) | HR 0.37 (95% CI 0.17–0.80)Planned subset analysis in the adolescent cohort (median follow-up 3.1 years, range 0.2 to 5.5, per the full text), labelled exploratory here. The authors report that no progression events occurred among the patients who discontinued part or all of N-AVD early (12 patients). |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| PFS | 0.45 | 0.3–0.65 |
| PFS | 0.24 | 0.09–0.63 |
| OS | 0.16 | 0.03–0.75 |
| PFS | 0.37 | 0.17–0.8 |
Appears in
Sources
Herrera AF, LeBlanc M, Castellino SM, Li H, Rutherford SC, Evens AM, et al. Nivolumab+AVD in Advanced-Stage Classic Hodgkin's Lymphoma. N Engl J Med. 2024;391(15):1379-1389.
Rutherford SC, Li H, Herrera AF, LeBlanc M, Ahmed S, Davison K, et al. Nivolumab-AVD Versus Brentuximab Vedotin-AVD in Older Patients With Advanced-Stage Classic Hodgkin Lymphoma Enrolled on S1826. J Clin Oncol. 2025;43(27):2968-2973.
Castellino SM, Li H, Herrera AF, LeBlanc M, Parsons SK, Unger JM, et al. Three-Year Follow-Up of Nivolumab-AVD Versus Brentuximab Vedotin-AVD in Adolescents With Advanced-Stage Classic Hodgkin Lymphoma on S1826. J Clin Oncol. 2026;44(6):449-454.