Outlining Common Drawbacks to Prior Standards for Hodgkin Lymphoma

Early studies identifying a signal with PD-1 blockade in patients with advanced Hodgkin lymphoma being treated in the frontline setting inspired the development of the phase 3 SWOG S1826 trial (NCT03907488), according to Alex Herrera, MD.¹

In a conversation with CancerNetwork®, Herrera, chief of the Division of Lymphoma in the Department of Hematology and Hematopoietic Cell Transplantation at City of Hope as well as associate medical director of the Briskin Center for Clinical Research, discussed the strengths and limitations of prior standards of care, contextualized by the March 2026 approval of nivolumab (Opdivo) plus doxorubicin, vinblastine, and dacarbazine (AVD), among patients with untreated stage III or IV Hodgkin lymphoma.²

He initially highlighted 2 common chemotherapy regimens, doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and in Europe, escalated doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP). He explained that these combination chemotherapy regimens were delivered for longer courses in patients with advanced disease, prompting the evaluation of brentuximab vedotin (Adcetris) in combination with doxorubicin, vinblastine, and dacarbazine (AVD). This regimen, although efficacious, conferred significantly more toxicity.

Contextualized by drawbacks of each regimen, as well as early studies with PD-1 blockade, Herrera’s team initiated the phase 3 trial, which compared nivolumab/AVD against brentuximab vedotin plus AVD.

Transcript:

For decades, the treatment of advanced stage classic Hodgkin lymphoma has been 1 of 2 traditional chemotherapy regimens: ABVD and, particularly in Germany or Europe, escalated BEACOPP. Patients with advanced stage Hodgkin lymphoma have typically received combination chemotherapy for longer courses than we might see in early-stage disease.

A few years ago, brentuximab vedotin, which is an antibody drug conjugate directed against CD30 on the surface of the Hodgkin lymphoma Reed-Sternberg cell was incorporated into the frontline treatment of advanced-stage Hodgkin lymphoma through the phase 3 ECHELON-1 study [NCT01712490] that showed that 6 cycles of brentuximab vedotin combined with AVD led to prolonged progression-free, and ultimately, overall survival [OS] compared with 6 cycles of ABVD.³

That approach, the brentuximab vedotin-AVD approach has some drawbacks. Even though it improved the efficacy of treatments compared with ABVD, it also increased the toxicity compared with standard ABVD: we saw more peripheral neuropathy, we saw an increase in the risk of febrile neutropenia [and] sepsis infections that necessitated the use of growth factor G-CSF, and it became incorporated into our treatment as an option for advanced stage Hodgkin lymphoma patients. But it had its drawbacks.

For pediatric patients with advanced stage Hodgkin lymphoma, there were some variations in these regimens––tweaks to the chemotherapy. Also, a majority…as high as 60% of [pediatric] patients with advanced stage Hodgkin lymphoma, received radiotherapy as part of their initial treatment. That was the context into which we waded into as we designed the SWOG S1826 trial.

[N]ivolumab and pembrolizumab [Keytruda] were [quite] effective in patients with relapsed/refractory Hodgkin lymphoma, and we were conducting studies over the years moving this PD-1 blockade, which was this very targeted therapy, in Hodgkin lymphoma earlier during therapy. There were some initial studies showing that even as part of frontline therapy, PD-1 blockade was effective and safe, but these were smaller studies. We designed the SWOG S1826 study to test whether in patients with advanced-stage classic Hodgkin lymphoma, stage III or IV disease, if nivolumab combined with AVD could lead to improved outcomes compared with the standard therapy, which in this case, the control arm was brentuximab vedotin combined with AVD.

References

1. FDA approves nivolumab with chemotherapy for previously untreated Hodgkin lymphoma. News release. FDA. March 20, 2026. Accessed April 20, 2026. https://tinyurl.com/4dxanszv
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