The eBEACOPP regimen, consisting of bleomycin, vincristine, procarbazine and prednisone plus escalated doses of etoposide, doxorubicin and cyclophosphamide, is a standard frontline treatment for classical Hodgkin lymphoma (cHL). This intensive regimen confers the highest primary cure rates but also considerable and often persistent treatment-related morbidities. Now, data from the HD21 trial demonstrate the improved risk-to-benefit ratio of a new regimen comprising the antibody–drug conjugate brentuximab vedotin plus etoposide, cyclophosphamide, doxorubicin, dacarbazine and dexamethasone (BrECADD).

In this phase III trial, 1,500 patients of 18–60 years of age with advanced-stage cHL were randomly assigned (1:1) to receive PET-guided treatment with BrECADD versus eBEACOPP, each for 4 cycles if PET-2 negative (Deauville score 1–3 after cycle 2) or 6 cycles if PET-2 positive (Deauville score 4–5). The co-primary end points were improved tolerability, defined by investigator-assessed treatment-related morbidity (acute grade 4 haematological or grade 3–4 non-haematological organ system toxicities), and non-inferior progression-free survival (PFS).