N-AVD or BrECADD for Advanced-Stage Classical Hodgkin Lymphoma: Choosing the Right Treatment for the Right Patient

Frontline therapy for advanced-stage classical Hodgkin lymphoma (cHL) has entered a new era. Two phase III trials have established highly effective but conceptually different strategies: nivolumab plus doxorubicin, vinblastine, and dacarbazine (N-AVD) in SWOG S1826 and PET-adapted BrECADD in GHSG HD21. Because these regimens were tested against different comparators and in different populations, their outcomes should not be interpreted as a head-to-head comparison. This review focuses on translating both trials into individualized treatment selection. N-AVD combines excellent disease control with relatively low hematologic toxicity, minimal use of radiotherapy, operational simplicity, and direct evidence across a broad age range, including patients older than 60 years. BrECADD provides mature disease-control data, PET2-guided treatment duration, potentially only 4 cycles in patients with complete metabolic response, lower anthracycline exposure in PET2-negative patients, and substantially improved gonadal recovery compared with eBEACOPP. The relevant trade-offs differ: hematologic and infectious toxicity, immune-related adverse events, fertility, long-term toxicity, radiotherapy exposure, PET availability, and health-system logistics may each influence regimen selection. Rather than identifying a universal winner, contemporary practice should define which patient is best suited to each strategy and incorporate shared decision-making into frontline treatment.