Brentuximab Vedotin Plus Chemo Wins EU Approval for Newly Diagnosed, Stage IIB-IV Hodgkin Lymphoma

The European Commission has approved brentuximab vedotin (Adcetris) in combination with etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone (BrECADD) for the treatment of adult patients with newly diagnosed, stage IIB to IV Hodgkin lymphoma.¹

This approval follows a positive opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use that was issued on April 25, 2025.

This regulatory decision was supported by data from the randomized phase 3 HD21 trial (NCT02661503), which evaluated BrECADD compared with the European standard of care (SOC) of escalated doses of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (eBEACOPP) in patients with Hodgkin lymphoma that was stage IIB with risk factors, stage III, or stage IV.

The trial met its co-primary efficacy and safety end points, showing superior treatment-related morbidity (TRMB) outcomes and noninferior progression-free survival (PFS) outcomes for BrECADD vs eBEACOPP. The rate of TRMB was 42% in patients who received BrECADD (n = 738) vs 59% of those given eBEACOPP (n = 732; relative risk, 0.72; 95% CI, 0.65-0.80; P < .0001).² Furthermore, at a median follow-up of 48 months, the estimated 4-year PFS rates in these arms were 94.3% (95% CI, 92.6%-96.1%) vs 90.9% (95% CI, 88.7%-93.1%), respectively (HR, 0.66; 95% CI, 0.45-0.97; P = .035). Additionally, the respective 4-year overall survival (OS) rates were 98.6% (95% CI, 97.7%-99.5%) vs 98.2% (95% CI, 97.2%-99.3%).

“With BrECADD, patients now have a treatment option that not only offers greater curative potential but also significantly reduces TRMB compared [with] eBEACOPP,” Peter Borchmann, MD, PhD, trial chairman of HD21 and assistant medical director in the Department of Haematology and Oncology at the University Hospital of Cologne in Germany, stated in a news release.¹ “This new [brentuximab vedotin]–based combination therapy may offer a new SOC for frontline treatment of adults with advanced-stage Hodgkin lymphoma, contributing to improved long-term outcomes for patients.”

The multi-country, prospective, open-label, multicenter HD21 trial was conducted by the German Hodgkin Study Group and employed a PET response–adapted design. The trial enrolled patients with newly diagnosed Hodgkin lymphoma that was stage IIB with a large mediastinal mass and/or extranodal lesions, stage III, or stage IV. Patients were randomly assigned to receive 2 cycles of either escalated BrECADD or BEACOPP, followed by interim PET staging, after which investigators decided whether patients should subsequently receive 2 or 4 cycles of escalated BrECADD or BEACOPP.

The co-primary end point of TRMB, which was assessed in terms of superiority, was a novel safety end point that considers clinically relevant acute toxicities associated with primary chemotherapy. PFS, the other co-primary end point, was assessed in terms of noninferiority. Secondary end points included complete response rate, OS, 1-year infertility rate, rate of second malignancies, frequency of adverse effects, therapy adherence, and quality of life.

“[The] approval represents a significant advancement for patients with Hodgkin lymphoma in the European Union [EU],” Teresa Bitetti, president of the Global Oncology Business Unit at Takeda, the developer of brentuximab vedotin, added in the news release. “This approval reinforces the role of [brentuximab vedotin] as a backbone in the treatment of specific lymphomas, offering health care professionals greater flexibility to tailor treatment plans according to individual patient needs. We’re proud to contribute another impactful option for those diagnosed with this challenging disease.”

In the EU, brentuximab vedotin is also approved for use with doxorubicin, vinblastine, and dacarbazine (AVD) in adult patients with previously untreated, CD30-positive, stage III or IV Hodgkin lymphoma; as monotherapy for adult patients CD30-positive Hodgkin lymphoma at increased risk of relapse or progression following autologous stem cell transplant (ASCT); and as monotherapy for adult patients with relapsed/refractory, CD30-positive Hodgkin lymphoma following ASCT or at least 2 prior therapies when ASCT or multi-agent chemotherapy are not treatment options.

Notably, brentuximab vedotin is currently FDA approved in combination with AVD for the first-line treatment of adult patients with stage III or IV classical Hodgkin lymphoma; in combination with doxorubicin, vincristine, etoposide, prednisone, and cyclophosphamide for the first-line treatment of pediatric patients at least 2 years of age with high-risk classical Hodgkin lymphoma; as monotherapy for adult patients with chronic Hodgkin lymphoma at high risk of relapse or progression following autologous hematopoietic stem cell transplant (auto-HSCT); and as monotherapy for adult patients with chronic Hodgkin lymphoma following progression on auto-HSCT or at least 2 prior multi-agent chemotherapy regimens in patients who are not candidates for auto-HSCT.

References

1. European Commission approves Adcetris (brentuximab vedotin) for the treatment of adult patients with newly diagnosed stage IIb/III/IV Hodgkin lymphoma in combination with ECADD. News release. Takeda. June 3, 2025. Accessed June 3, 2025. https://www.takedaoncology.com/news/news-releases/europe-adcetris-approval/
2. Borchmann P, Ferdinandus J, Schneider G, et al. Assessing the efficacy and tolerability of PET-guided BrECADD versus eBEACOPP in advanced-stage, classical Hodgkin lymphoma (HD21): a randomised, multicentre, parallel, open-label, phase 3 trial. Lancet. 2024;404(10450):341-352. doi:10.1016/S0140-6736(24)01315-1