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10 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.
Advanced-stage classical Hodgkin lymphoma is Hodgkin lymphoma involving nodes on both sides of the diaphragm or organs such as the liver, lungs or bone marrow. It is treated with six cycles of combination chemotherapy, and two trials changed the standard: replacing bleomycin with brentuximab vedotin (ECHELON-1) and then with nivolumab (SWOG S1826), which cured more patients with less toxicity.
Advanced classical Hodgkin lymphoma was the first disseminated cancer cured by chemotherapy, with MOPP in the 1960s and then ABVD from 1975, and for forty years the argument was between ABVD and the more intensive escalated BEACOPP of the German Hodgkin Study Group, which cures more patients up front at the cost of infertility, leukaemia and toxicity. PET-adapted therapy eased the trade-off: the RATHL trial (New England Journal of Medicine 2016) showed bleomycin can be dropped after two cycles in PET-negative patients without loss of efficacy, and HD18 showed escalated BEACOPP can be shortened to four cycles in PET-negative patients. The International Prognostic Score, the Deauville score on interim PET and baseline metabolic tumour volume stratify risk.
Two trials then rebuilt the regimen. ECHELON-1 (New England Journal of Medicine 2018) randomised 1,334 patients to ABVD or to brentuximab vedotin with AVD (A+AVD), replacing bleomycin with the CD30 antibody-drug conjugate; modified progression-free survival improved and, in the six-year update (New England Journal of Medicine 2022), overall survival was higher with A+AVD (93.9 against 89.4 percent), the first survival gain in advanced Hodgkin lymphoma in a generation. SWOG S1826 (New England Journal of Medicine 2024) then randomised 994 patients aged 12 and over to A+AVD or to nivolumab with AVD (N+AVD): one-year progression-free survival was 94 against 86 percent with fewer peripheral neuropathy and infection problems and almost no radiotherapy, making N+AVD the preferred regimen in the NCCN guideline for adults and adolescents. In Europe, GHSG HD21 (Lancet 2024) showed that BrECADD, a brentuximab-containing variant of escalated BEACOPP, was less toxic and at least as effective as escalated BEACOPP with four-year progression-free survival of 94.3 against 90.9 percent, giving a second intensive PET-guided option. Paediatric groups are testing brentuximab vedotin and PD-1 antibodies in children with advanced disease, older patients receive AVD-based or brentuximab-sequenced regimens because bleomycin and BEACOPP are too toxic, and consolidation radiotherapy is now limited to residual PET-positive bulky disease.
| Setting | Approach | Guideline |
|---|---|---|
| Staging and risk | FDG-PET/CT with Lugano staging, International Prognostic Score, fertility counselling and cardiac and pulmonary baselines. | not mapped |
| First line, adults and adolescents 12 and over | Nivolumab with AVD for six cycles (SWOG S1826, preferred); brentuximab vedotin with AVD (ECHELON-1) as an alternative; PET-adapted ABVD with bleomycin omission after two cycles (RATHL) where antibodies are unavailable. | not mapped |
| First line, intensive European option | BrECADD for four to six cycles guided by interim PET (GHSG HD21), replacing escalated BEACOPP. | not mapped |
| Children | Response-adapted Children's Oncology Group or EuroNet regimens; brentuximab vedotin with AVD in advanced paediatric disease; radiotherapy for slow responders only. | not mapped |
| Older or frail patients | AVD with brentuximab vedotin sequenced before and after, or nivolumab-AVD; avoid bleomycin and BEACOPP. | not mapped |
| End of treatment | PET-directed consolidation radiotherapy only for residual PET-positive bulky disease; long-term survivorship follow-up. | not mapped |
| Advanced Hodgkin lymphoma in the United States: nivolumab with AVD | 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 |
| Advanced Hodgkin lymphoma in Germany and much of Europe: PET-guided BrECADD | 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. | not mapped |