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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.
Averages across everyone diagnosed, often years ago. A median is the middle of a group: half the people counted lived longer than the figure shown, and some lived far longer. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.
About half of classical Hodgkin lymphoma at diagnosis; most patients are cured, but a fifth to a quarter relapse after ABVD, and older patients fare worse.
Leukaemias, myeloma and MDS live in the marrow and blood; lymphomas grow in lymph nodes and spleen. The node stations are the disease map, not a route of spread, and staging counts them.
In lymphoma the node stations are the disease itself; staging (Ann Arbor / Lugano) counts how many regions and sides of the diaphragm are involved.
Same organ: High-grade B-cell lymphoma with MYC and BCL2 rearrangements (double-hit lymphoma), Mediastinal grey zone lymphoma, Primary effusion lymphoma, Plasmablastic lymphoma, T-cell/histiocyte-rich large B-cell lymphoma, EBV-positive diffuse large B-cell lymphoma, Primary large B-cell lymphoma of the testis, Gastric MALT lymphoma, Ocular adnexal MALT lymphoma, Extranodal NK/T-cell lymphoma, Adult T-cell leukaemia/lymphoma, ALK-positive anaplastic large cell lymphoma, ALK-negative anaplastic large cell lymphoma, Breast implant-associated anaplastic large cell lymphoma, Primary cutaneous anaplastic large cell lymphoma, Lymphomatoid papulosis, Mycosis fungoides, Enteropathy-associated T-cell lymphoma, Monomorphic epitheliotropic intestinal T-cell lymphoma, Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma), Splenic marginal zone lymphoma, Nodal marginal zone lymphoma, Primary cutaneous marginal zone lymphoma, Primary cutaneous follicle centre lymphoma, Sezary syndrome, Nodal T-follicular helper cell lymphoma, angioimmunoblastic type (angioimmunoblastic T-cell lymphoma), Hepatosplenic T-cell lymphoma, Intravascular large B-cell lymphoma, Lymphomatoid granulomatosis, T-cell prolymphocytic leukaemia, Splenic B-cell lymphoma/leukaemia with prominent nucleoli (formerly B-cell prolymphocytic leukaemia and hairy cell leukaemia variant), T-cell large granular lymphocytic leukaemia, Mixed-phenotype acute leukaemia, Myeloid leukaemia of Down syndrome, Burkitt leukaemia, Marginal zone lymphoma, Cutaneous T-cell lymphoma (mycosis fungoides and Sezary syndrome), Primary mediastinal (thymic) large B-cell lymphoma, Leukaemia (all types), Acute myeloid leukaemia, Acute lymphoblastic leukaemia, Chronic lymphocytic leukaemia, Chronic myeloid leukaemia (CML), Diffuse large B-cell lymphoma, Follicular lymphoma, Hodgkin lymphoma, Mantle cell lymphoma, Multiple myeloma, Non-Hodgkin lymphoma (all types), Myelodysplastic syndromes / neoplasms (MDS), Myeloproliferative neoplasms (PV, ET, myelofibrosis), Polycythaemia vera (PV), Essential thrombocythaemia (ET), Waldenström macroglobulinaemia, Hairy cell leukaemia, Peripheral T-cell lymphomas (including cutaneous T-cell lymphoma), Blastic plasmacytoid dendritic cell neoplasm (BPDCN), Burkitt lymphoma, HIV-associated (AIDS-related) lymphomas, Chronic myelomonocytic leukaemia and MDS/MPN overlap neoplasms, Systemic mastocytosis, Erdheim-Chester disease, Rosai-Dorfman disease and other histiocytic neoplasms, Langerhans cell histiocytosis (LCH), Post-transplant lymphoproliferative disorder (PTLD), FLT3-mutated acute myeloid leukaemia, IDH1- and IDH2-mutated acute myeloid leukaemia, NPM1-mutated and KMT2A-rearranged acute myeloid leukaemia, Secondary and therapy-related acute myeloid leukaemia, Acute promyelocytic leukaemia, Acute myeloid leukaemia in older or unfit patients, Smouldering multiple myeloma, Newly diagnosed multiple myeloma, transplant-eligible, Newly diagnosed multiple myeloma, transplant-ineligible, Relapsed or refractory multiple myeloma, Plasma cell leukaemia, Lower-risk myelodysplastic syndromes, Higher-risk myelodysplastic syndromes, Chronic lymphocytic leukaemia, first treatment, Relapsed or refractory chronic lymphocytic leukaemia, Richter transformation of chronic lymphocytic leukaemia, Chronic myeloid leukaemia, chronic phase, Chronic myeloid leukaemia, accelerated and blast phase, Primary myelofibrosis, Standard-risk B-cell acute lymphoblastic leukaemia in children, High-risk acute lymphoblastic leukaemia in children (high-risk B-ALL and T-ALL), Philadelphia chromosome-positive acute lymphoblastic leukaemia in children (Ph-positive ALL), Philadelphia chromosome-like acute lymphoblastic leukaemia (Ph-like or BCR::ABL1-like ALL), Infant acute lymphoblastic leukaemia (KMT2A-rearranged, under one year), Relapsed and refractory acute lymphoblastic leukaemia in children, Acute myeloid leukaemia in children, Erdheim-Chester disease, Rosai-Dorfman-Destombes disease, Single-system Langerhans cell histiocytosis (bone, skin or one other organ), Multisystem Langerhans cell histiocytosis (with or without risk-organ involvement), Indolent and smouldering systemic mastocytosis, Advanced systemic mastocytosis (aggressive SM, SM with an associated haematological neoplasm, mast cell leukaemia), Early-stage classical Hodgkin lymphoma (stage I to II), Nodular lymphocyte-predominant Hodgkin lymphoma (nodular lymphocyte-predominant B-cell lymphoma), Relapsed and refractory classical Hodgkin lymphoma
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FDG-PET/CT with Lugano staging, International Prognostic Score, fertility counselling and cardiac and pulmonary baselines.
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.
BrECADD for four to six cycles guided by interim PET (GHSG HD21), replacing escalated BEACOPP.
Response-adapted Children's Oncology Group or EuroNet regimens; brentuximab vedotin with AVD in advanced paediatric disease; radiotherapy for slow responders only.
AVD with brentuximab vedotin sequenced before and after, or nivolumab-AVD; avoid bleomycin and BEACOPP.
PET-directed consolidation radiotherapy only for residual PET-positive bulky disease; long-term survivorship follow-up.
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.
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.
The two regimens that the current standards displaced are still used, and still reasonable where the newer ones are not available. ABVD with PET adaptation. RATHL enrolled 1,214 patients and showed that in those whose PET after two cycles was negative, bleomycin could be omitted from cycles 3 to 6 without loss of control: three-year progression-free survival 85.7 per cent for continued ABVD against 84.4 per cent for AVD, with less lung toxicity. This remains common British practice and is a perfectly defensible treatment. Brentuximab vedotin with AVD. ECHELON-1 randomised 1,334 patients with untreated stage III or IV disease to A+AVD or ABVD: two-year modified progression-free survival was 82.1 against 77.2 per cent (hazard ratio 0.77) and, at six years, overall survival was 93.9 against 89.4 per cent (hazard ratio 0.59). It is the only first-line trial in advanced Hodgkin lymphoma to show an overall survival advantage. The cost is peripheral neuropathy, which is commoner and more severe than with ABVD; in SWOG S1826 any-grade peripheral neuropathy was 54.2 per cent with brentuximab-AVD against 28.1 per cent with nivolumab-AVD. Growth-factor support is mandatory. In England, NICE TA1059 recommends brentuximab vedotin with doxorubicin, dacarbazine and vinblastine for untreated stage 3 or 4 CD30-positive Hodgkin lymphoma in adults, so this is the regimen that is funded first line; there is no NICE appraisal of nivolumab with AVD. Older and frail patients tolerate none of these well. Options are ABVD with bleomycin omitted, sequential brentuximab vedotin before and after AVD, or a reduced-intensity regimen, and the choice is made on comorbidity rather than on chronological age.
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For fit younger patients treated in the intensive German tradition, BrECADD replaces escalated BEACOPP; how it compares with nivolumab-AVD from S1826 is the open question.
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.
Brentuximab vedotin with AVEPC is the new standard for high-risk paediatric Hodgkin lymphoma and led to the first paediatric approval of the drug in November 2022.
Confirmation, by a different route from HD18, that the interim scan can safely direct de-escalation in advanced Hodgkin lymphoma, and that most of the toxicity of escalated BEACOPP can be avoided in the 84 per cent of patients who respond early.
ECHELON-1 made a targeted antibody-drug conjugate part of first-line Hodgkin therapy and eventually showed that this saves lives, not just relapses. It set the reference arm against which nivolumab-AVD (SWOG S1826) and BrECADD (HD21) were later compared. Neuropathy is the main price and needs proactive dose modification.
The basis for four cycles of escalated BEACOPP as the German standard when the interim scan is negative, and the reason rituximab was abandoned as an addition to that regimen. The authors recommend the scan-guided strategy for all patients with advanced-stage disease.
An interim PET scan after two cycles guides treatment of advanced Hodgkin lymphoma: drop bleomycin if negative, intensify if positive.
The reason cardiac surveillance belongs in Hodgkin lymphoma survivorship care, the reason smoking cessation is a specific intervention for this group rather than general advice, and part of the reason modern protocols try to limit both mediastinal radiation and cumulative anthracycline dose.
Query for this cancer: (TITLE:"Advanced-stage classical Hodgkin lymphoma" OR ABSTRACT:"Advanced-stage classical Hodgkin lymphoma" OR TITLE:"stage III to IV" OR ABSTRACT:"stage III to IV" OR TITLE:"Stage III to IV classical Hodgkin lymphoma" OR ABSTRACT:"Stage III to IV classical Hodgkin lymphoma" OR TITLE:"Advanced Hodgkin lymphoma" OR ABSTRACT:"Advanced Hodgkin lymphoma" OR TITLE:"Disseminated Hodgkin lymphoma" OR ABSTRACT:"Disseminated Hodgkin lymphoma" OR TITLE:"High-risk Hodgkin lymphoma IPS 4 or more" OR ABSTRACT:"High-risk Hodgkin lymphoma IPS 4 or more") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Advanced-stage classical Hodgkin lymphoma (stage III to IV), not a curated reading list.
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Bleeding that does not stop by itself, bleeding from more than one site, or new bruising in several places or one large area.
Breathing very fast, confusion or slurred speech, blue, pale or blotchy skin, a very high or very low temperature, shivering, or a rash that does not fade when pressed: the NHS says call 999 or go to A and E, and do not drive yourself.
Any new neurological symptom that is not explained. Brentuximab vedotin carries a boxed warning for progressive multifocal leukoencephalopathy, a brain infection; the label says to hold the drug and investigate at the first suspicion.
Persistent headache with extreme tiredness, nausea, dizziness on standing or low blood pressure. Vomiting, severe weakness or collapse is adrenal crisis.
Macmillan lists difficulty passing urine, loss of bladder or bowel control and constipation among the signs of spinal cord compression and says to contact the hospital straight away. If you cannot reach anyone, go to A and E and say you have lymphoma and symptoms of spinal cord compression.
These are the signs that the airway or the brain is being affected rather than only the veins. The triage standard sends shortness of breath at rest and any altered level of consciousness straight to 999.
See all on the product pages:BleomycinBrentuximab vedotinCentral venous access (port, PICC line)CyclophosphamideDacarbazineDoxorubicinEtoposideFebrile neutropeniaHypogammaglobulinaemia and infection risk after B-cell therapiesMetastatic spinal cord compression (MSCC)NeutropeniaNivolumabProcarbazineSuperior vena cava obstructionVinblastineVincristine·Printable cards in the navigator
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