What changed: Advanced-stage classical Hodgkin lymphoma (stage III to IV)

When this page itself was last checked or edited.

4-year PFS 94.

A milestone in how this cancer is treated.

2-year PFS 92% vs 83%, HR 0.

Three-year event-free survival 92.

A milestone in how this cancer is treated.

Five-year progression-free survival 85.

A milestone in how this cancer is treated.

6-year OS 93.

Four cycles of escalated BEACOPP non-inferior to six or eight after a negative scan (five-year progression-free survival 92.

3-year PFS 85.

A milestone in how this cancer is treated.

GHSG HD21 randomised about 1,500 patients aged 18 to 60 with untreated advanced-stage classical Hodgkin lymphoma to PET-guided BrECADD or PET-guided escalated BEACOPP. Four-year progression-free survival was 94.3 against 90.9 per cent (hazard ratio 0.66) and treatment-related morbidity, a composite of organ toxicity, infection and haematological toxicity, was 42 against 59 per cent. BrECADD replaces the bleomycin, vincristine and procarbazine of escalated BEACOPP with brentuximab vedotin and dacarbazine, which removes the lung toxicity, most of the neuropathy and much of the infertility risk, and PET guidance means most patients receive four cycles rather than six. This is the highest progression-free survival reported in advanced Hodgkin lymphoma. It is also intensive treatment that requires an experienced unit, hospital admission for febrile neutropenia in a substantial minority, and growth-factor support throughout. The earlier PET-guided BEACOPP trials, HD18 and AHL2011, established the principle: HD18 reduced treatment from eight cycles to four in PET-negative patients, and AHL2011 switched PET-negative patients from escalated BEACOPP to ABVD, in both cases without losing disease control.

A milestone in how this cancer is treated.

A milestone in how this cancer is treated.

A milestone in how this cancer is treated.

SWOG S1826 randomised 994 patients aged 12 and over with untreated stage III or IV classical Hodgkin lymphoma to nivolumab with AVD or to brentuximab vedotin with AVD, the regimen that had itself displaced ABVD. Two-year progression-free survival was 92 against 83 per cent (hazard ratio 0.45), and any-grade peripheral neuropathy was 28.1 against 54.2 per cent. It is the first trial in this disease to include adolescents and adults in a single protocol, and the FDA approved nivolumab with doxorubicin, vinblastine and dacarbazine for previously untreated stage III or IV classical Hodgkin lymphoma in adults and children of 12 and over on 20 March 2026, converting the two earlier relapsed-disease accelerated approvals to traditional approval at the same time. It is a genuinely gentler regimen as well as a more effective one: less neuropathy, less growth-factor requirement, and no bleomycin. The subset analysis of the 99 eligible patients aged 60 and over reported two-year progression-free survival of 89 per cent with nivolumab-AVD against 64 per cent with brentuximab-AVD (hazard ratio 0.24) and two-year overall survival of 96 against 85 per cent (hazard ratio 0.16), with non-relapse mortality of 6 against 16 per cent, 55 per cent discontinuing brentuximab vedotin against 14 per cent discontinuing nivolumab, and six cycles delivered without dose reduction in 69 against 26 per cent. That matters, because older patients tolerate brentuximab-AVD badly and are the group in which first-line treatment most often fails. What is not yet known: overall survival has not separated, follow-up is short for a disease measured in decades, and the long-term consequences of PD-1 blockade in a 20-year-old who will live another 60 years are unknown. That last point is the honest counter-argument to adopting it everywhere. (NCCN Category 1)