S1826 Trial Results Summary

Overview

• Brentuximab vedotin plus standard chemotherapy (usual treatment)
• Nivolumab plus standard chemotherapy (study treatment)

The study asked which treatment plan helped people live longer without the cancer getting worse.

What we learned

Compared to people who got brentuximab vedotin plus standard chemotherapy, people who got nivolumab plus standard chemotherapy:

• Were less likely to have the cancer come back or get worse within 2 years of starting treatment
• Had fewer side effects — and less serious side effects

And fewer people who got nivolumab plus standard chemotherapy died within 2 years of starting treatment.

Why this study matters

It’s common for doctors to treat classic Hodgkin lymphoma with brentuximab vedotin plus standard chemotherapy. But this treatment combination doesn’t work for everyone, and it can cause many side effects.

S1826 found that nivolumab plus standard chemotherapy worked better — and caused fewer side effects. The U.S. Food and Drug Administration (FDA) then approved this treatment combination for people with advanced-stage classic Hodgkin lymphoma. This could give more people with classic Hodgkin lymphoma a treatment option that works for them.

Detailed Trial Results

What was the trial about?

The S1826 clinical trial compared 2 treatment plans for adults and adolescents with newly diagnosed, advanced-stage classic Hodgkin lymphoma. (“Advanced-stage” means the lymphoma has spread, possibly outside the lymph nodes.) Both plans used a chemotherapy treatment called AVD, which combines 3 drugs: doxorubicin (also known as Adriamycin), vinblastine, and dacarbazine.

For classic Hodgkin lymphoma, doctors usually add the drug brentuximab vedotin to AVD. The S1826 trial asked if replacing brentuximab vedotin with nivolumab could improve treatment.

Why was the study important?

Brentuximab vedotin releases chemotherapy inside lymphoma cells to attack the cancer. When combined with AVD, it can work well to cure people with classic Hodgkin lymphoma.

But for some people, the lymphoma comes back or doesn’t respond to the treatment. Side effects can also be a problem for many people. The S1826 trial was an important step in finding treatments that work better for newly diagnosed patients — and cause fewer or less serious side effects.

Nivolumab is an immunotherapy drug that helps the immune system attack cancer by targeting a certain protein in white blood cells. Before the S1826 trial, nivolumab was approved by the Food and Drug Administration (FDA) to treat classic Hodgkin lymphoma that came back or got worse after other treatments but not approved for newly diagnosed classic Hodgkin lymphoma.

What were the goals of the study?

The study was set up to find out:

Who took part in the study?

People joined the study at 256 hospitals in the United States and Canada.

970 of them met all study requirements and were included in the analysis of study findings. Everyone in the study was newly diagnosed with stage 3 or 4 classic Hodgkin lymphoma and had not gotten treatment yet. People with an autoimmune disease were not able to join the study.

What happened during the study?

People were randomly assigned to one of 2 treatment groups:

Less than 1 percent of people in the study also got radiation treatment after finishing BV-AVD or N-AVD treatment.

The study team monitored patients’ health and how the cancer responded to treatment. They tracked if the cancer got better, got worse, or stayed the same.

They also tracked side effects and health problems.

Study results

N-AVD was better than BV-AVD at controlling classic Hodgkin lymphoma.

After 2 years, the study team compared how many people in each treatment group did not have the cancer come back or get worse.

N-AVD helped people avoid problems for longer than BV-AVD did.

For all people in the study, the study team watched to see if:

• The cancer came back or got worse
• The patient got treatment that was not part of the study’s treatment plan, even though the cancer did not get worse
• The patient died without the cancer getting worse

These things were less likely to happen to people who got N-AVD than people who got BV-AVD.

Overall, people who got N-AVD had fewer side effects — and less serious side effects — than people who got BV-AVD.

More people in the BV-AVD treatment group stopped treatment early — most often because of side effects.

Age was an important factor in the BV-AVD treatment group. People who were older than 60 and got BV-AVD were more likely than younger people to stop treatment because of side effects.

In the N-AVD group, side effects were similar across all ages.

2 years after starting treatment, fewer people in the N-AVD treatment group had died.

Infection was the most common cause of death in both groups. 3 people in the study died from lymphoma.

How has this study helped patients and researchers?

The S1826 trial showed that adolescents and adults benefited more from using nivolumab with AVD chemotherapy than brentuximab vedotin with AVD chemotherapy. After 2 years, N-AVD controlled the cancer better, helped people live longer without major problems from cancer, and caused fewer side effects. Based on these results, the U.S. Food and Drug Administration (FDA) approved N-AVD for treating advanced-stage classic Hodgkin lymphoma in adolescents and adults.

BV-AVD has worked well for many but not all people with classic Hodgkin lymphoma. So finding a treatment that may work for more people is encouraging for patients and doctors. With fewer side effects, N-AVD could allow more people to finish treatment. This may be especially important for older patients, who were more likely than younger patients to stop BV-AVD treatment early because of side effects.

The study team will track how people in the study are doing for up to 10 years in total. The longer follow-up will help the team learn about patients’ health beyond the 2-year mark. This may lead to other important study results about N-AVD and BV-AVD.

How to learn more

• Visit clinicaltrials.gov/study/NCT03907488
• Read the report in the New England Journal of Medicine at doi.org/10.1056/NEJMoa2405888
• Talk with your doctor if you have questions

Thank you!

We’re grateful to everyone who joined this trial and made it possible. Trials like this one help answer important questions that will make cancer care better for future patients.

The S1826 clinical trial was sponsored by SWOG Cancer Research Network and funded by the National Cancer Institute (NCI), part of the National Institutes of Health. The trial was conducted through the NCI’s National Clinical Trials Network.

This results summary was published on July 28, 2026. Newer information may have become available since that time.