ORLANDO, Fla. — A pair of studies offer new insights into treatments for newly diagnosed advanced-stage Hodgkin lymphoma (ASHL). One confirmed that long-term outcomes for the regimen known as nivolumab plus doxorubicin, vinblastine, and dacarbazine (N-AVD) continue to outperform the brentuximab vedotin and AVD (BV-AVD) regimen. The other study showed that a newer treatment approach, referred to as brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone (BrECADD), more commonly used in Europe than in the US, beats the elevated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (eBEACOPP) regimen.

The lead authors of these studies presented their findings at the American Society of Hematology (ASH) 2025 Annual Meeting.

The 3-year follow-up of the S1826 study showed continued superior outcomes in 970 patients with ASHL taking N-AVD vs BV-AVD. Over 3 years, the progression-free survival (PFS) rates were 91% and 82%, respectively, according to the abstract presented by Alex Herrera, MD, hematologist-oncologist and head of the Division of Lymphoma at City of Hope Comprehensive Cancer Center, Duarte, California, at the meeting.

The open-label, randomized, phase 3 HD21 trial assigned 1500 patients with ASHL aged 18-60 years to PET-guided BrECADD or eBEACOPP.

The trial’s final analysis found that the absolute 5-year PFS rate for BrECADD was 93.6% vs 90.6% for eBEACOPP, according to the abstract presented by Justin Ferdinandus, MD, resident physician of the University of Cologne, Cologne, Germany.

“N-AVD is well tolerated and is currently a frontline standard-of-care option for patients with ASHL in the US,” said ASH session co-moderator Michele Stanchina, DO, a hematologist-oncologist and assistant professor at the University of Miami/Sylvester Comprehensive Cancer Center, Miami, in an interview with Medscape Medical News. “However, considering the 5-year follow-up data of the HD21 trial, I think we will also start to see more clinicians utilizing the BrECADD regimen in the US in the future.”

“For many years, the standard of care for ASHL was based on the RATHL trial, where newly diagnosed patients were given two cycles of ABVD [doxorubicin, bleomycin, vinblastine, and dacarbazine] and then underwent interim PET-CT restaging. Patients with a positive interim PET-CT were then given eBEACOPP,” Stanchina explained.

However, eBEACOPP is linked to many adverse effects, she said, and the US moved toward AVD-based regimens. Meanwhile, a German study group designed BrECADD as a better alternative to eBEACOPP, she said.

S1826 Trial Results

In the extended S1826 trial, 970 patients comprised the modified intention-to-treat cohort. During his presentation, Herrera, the study’s lead author, shared data for multiple age groups:

• In adolescents, PFS was 93% for N-AVD vs 82% for BV-AVD.

• In adults aged 18-60 years, PFS rates were 91% and 85%, respectively. 

• In adults older than 60 years, there was a “marked difference” with PFS rates of 82% and 58%, respectively.

“The overall survival data are not yet mature,” Herrera cautioned, but at 3-year follow-up, there were 15 deaths in the BV-AVD arm and eight in the N-AVD arm. 

In an interview with Medscape Medical News, co-author Jonathan W. Friedberg, MD, MMSc, director of the Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, New York, said that with now more than 3 years of median follow-up, the hazard ratios remain the same, and over 90% of patients treated with N-AVD remain alive and disease-free.

He said N-AVD is cheaper than BV-AVD and doesn’t require growth factors. The FDA has not yet approved the therapy, but “as N-AVD is listed as a category 1 recommendation in NCCN [National Comprehensive Cancer Network] guidelines, insurance coverage is generally not an issue,” he continued.

In his presentation of the HD21 results, lead author Ferdinandus said BrECADD “offers an excellent long-term efficacy and tolerability profile, supporting its role as a preferred frontline treatment regimen within a PET-adapted treatment strategy.”

Ferdinandus told Medscape Medical News in an interview that the difference in PFS between BrECADD (94%) and eBEACOPP (91%) is “clinically meaningful in a disease where every relapse may require intensive salvage therapy or transplantation.”

Toxicity- and Cost-Related Factors

“For patients, the major impact is twofold: first, a higher chance of being cured with first-line therapy, and a lower risk of serious long-term toxicities, including infertility and therapy-associated AML/MDS [acute myeloid leukemia/myelodysplastic syndromes],” Ferdinandus said.

As for cost, brentuximab vedotin increases the upfront drug costs vs eBEACOPP. “However, BrECADD may reduce overall healthcare costs by preventing fertility loss, lowering long-term complication rates, and avoiding costs associated with relapse,” he noted.

In regard to availability, BrECADD is not FDA-approved, and “we do not have information on the current status or timing of a regulatory submission,” he said.

Takeda funded the HD21 study. The National Cancer Institute and Bristol Myers Squibb funded the S1826 study.

Herrera reported having relationships with Regeneron, Lilly, Allogene, AstraZeneca, Caribou, Seagen, Bristol Myers Squibb, Pfizer, Adicet Bio, ADC, Karyopharm, Tubulis, Merck, Takeda, AbbVie, City of Hope, Genmab, Kite, Genentech, and Gilead.

Ferdinandus reported having relationships with Roche, Takeda, and Pfizer. Friedberg reported having no disclosures.

Other study authors reported having various relationships. Stanchina reported having a relationship with Pfizer.