SWOG S1826: nivolumab plus AVD chemotherapy versus brentuximab-AVD for advanced Hodgkin lymphoma in adolescents and adults
Adding a PD-1 antibody to chemotherapy beat the brentuximab-based standard, with 92% of patients progression-free at two years and less nerve damage.
S1826 was a phase 3 trial run jointly by adult and paediatric cooperative groups, randomising 994 patients aged 12 and over with newly diagnosed stage III or IV classical Hodgkin lymphoma to nivolumab plus AVD (N-AVD) or brentuximab vedotin plus AVD (BV-AVD) for six cycles. Radiotherapy was discouraged and given to under 1%. The primary endpoint was PFS. At two years PFS was 92% versus 83% (hazard ratio 0.45), with benefit across ages including patients over 60. N-AVD caused less peripheral neuropathy and fewer treatment discontinuations, while immune-related events (mainly thyroid dysfunction and rash) were mostly low grade.
- 994 patients aged 12 and over (about a quarter under 18) with stage III-IV classical Hodgkin lymphoma; N-AVD vs BV-AVD.
- 2-year PFS 92% vs 83%; hazard ratio 0.45.
- Benefit consistent in adolescents, adults and patients over 60.
- Less peripheral neuropathy and fewer discontinuations with N-AVD; immune-related adverse events mostly grade 1-2.
- Consolidative radiotherapy used in fewer than 1% of patients.
S1826 moved checkpoint blockade into first-line Hodgkin lymphoma and made N-AVD a preferred regimen for advanced disease in patients from adolescence to older age, while removing radiotherapy for most. It also showed the value of a single trial spanning paediatric and adult groups. Longer follow-up is needed for overall survival and late immune effects in young patients.
- Overall survival data are immature; both arms have high survival.
- Follow-up is short for a disease where late relapses and second cancers matter.
- Comparison is with BV-AVD, not the European BrECADD regimen.
- Nivolumab cost and access limit adoption in some health systems.
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