Real-world outcomes of nivolumab-AVD and brentuximab vedotin-AVD in paediatric and adult advanced-stage Hodgkin lymphoma.

Brentuximab vedotin (BV)-doxorubicin, vinblastine and dacarbazine (AVD) and nivolumab (N)-AVD have transformed the frontline treatment of advanced-stage Hodgkin lymphoma (HL), yet real-world comparative data remain limited. In this multicentre retrospective study across 17 US centres, 646 patients treated between September 2011 and April 2025 were included; 509 (78.8%) received BV-AVD and 137 (21.2%) received N-AVD. Dose reductions or omissions were more common with BV-AVD (35.8% vs. 14.4%, p < 0.0001). N-AVD was associated with higher rates of neutropenia (any grade 77.2% vs. 43.9%, p < 0.0001; grade ≥3 58.1% vs. 34.0%, p < 0.0001) and infections (31.9% vs. 19.7%, p = 0.004), while grade ≥3 infections and febrile neutropenia were comparable. Neuropathy was significantly more frequent with BV-AVD (57.2% vs. 20.6%, p < 0.0001). End-of-therapy complete response rates were numerically higher with N-AVD (86.2% vs. 79.3%, p = 0.11). With a median follow-up of 26.8 months, 2-year overall survival (OS) was 97% for BV-AVD and 100% for N-AVD (p = 0.08) and 2-year progression-free survival (PFS) was 84% vs. 88% (p = 0.06). Survival outcomes were consistent in a 1:1 propensity score-matched cohort. These real-world data demonstrate comparable survival between regimens, with numerically improved PFS supporting N-AVD as a frontline standard for advanced-stage HL; however, higher rates of neutropenia and infections warrant careful monitoring and consideration of growth factor prophylaxis.