Teaching pack: Hodgkin lymphoma

Classical Hodgkin lymphoma is a B-cell cancer in which rare, giant Reed-Sternberg cells (about 1% of the mass) recruit an inflammatory microenvironment and hide behind amplified PD-L1. It peaks in young adults and again after 55, is staged with PET-CT and the Lugano system, and is cured in more than 85% of patients overall and in over 90% of early-stage disease. Because most patients are young and will live for decades, the field's defining problem is not cure but the cost of cure: anthracycline heart disease, bleomycin lung injury, infertility, and second cancers from alkylators and radiation.

That is why Hodgkin lymphoma pioneered response-adapted therapy. Interim PET after two cycles (Deauville score) steers de-escalation (drop bleomycin after negative PET2 in RATHL; omit radiotherapy in early stage in HD16/HD17/RAPID at a small PFS cost) or escalation to BEACOPP-type regimens. Two ADC- and immunotherapy-based regimens then replaced ABVD for advanced disease: brentuximab vedotin-AVD (ECHELON-1, overall survival benefit) and, from March 2026, nivolumab-AVD (SWOG S1826, PFS HR 0.45 versus BV-AVD, neuropathy halved, children and adults together). In Europe, GHSG HD21's PET-guided BrECADD matches escalated BEACOPP's ~94% PFS with far less toxicity. Relapse is treated with PD-1 blockade (pembrolizumab beat brentuximab in KEYNOTE-204), brentuximab, salvage chemotherapy and autologous transplant, with brentuximab consolidation for high-risk patients (AETHERA); allogeneic transplant and CD30 CAR-T are options for the few who fail everything.

• Immunotherapy in first line with less toxicity.
• Nivolumab-AVD is the new frontline standard for advanced disease (S1826: 2-year PFS 92%, neuropathy halved), approved March 2026 for ages 12 and up.
• Two intensive but de-toxified European options: PET-guided BrECADD (HD21) achieves ~94% 5-year PFS with 40% less morbidity than eBEACOPP.
• Interim PET steers therapy for nearly every patient: bleomycin omission (RATHL), radiotherapy omission (HD16/17, RAPID), cycle number (HD18, HD21).
• Radiotherapy is disappearing from advanced-stage care (<1% in S1826) and being minimised in early stage.
• PD-1 blockade is the most effective single agent in any lymphoma relapse (ORR ~70%), and beat brentuximab head to head (KEYNOTE-204).

1. 1832Thomas Hodgkin describes the disease; Reed and Sternberg characterise the cell (1898-1902)
2. 1950Peters shows extended-field radiotherapy can cure early-stage disease
3. 1964MOPP: first combination chemotherapy cure
4. 1964MOPP: the first combination chemotherapy to cure an advanced cancer (DeVita, NCI)
5. 1975ABVD introduced (Bonadonna); becomes global standard by the 1990s
6. 1992Escalated BEACOPP developed by the German Hodgkin Study Group
7. 2000Autologous transplant standard for relapse; late-effects registries reveal cardiac and second-cancer burden
8. 2011Brentuximab vedotin approved
9. 2011Brentuximab vedotin approved for relapsed disease; CD30 validated as an ADC target
10. 2014Lugano classification formalises PET staging and the Deauville scale

• AHOD2131 (COG / NCTN) (trial)
• Chemotherapy-free Hodgkin lymphoma: brentuximab + PD-1 in early stage (idea)
• CD30 CAR-T for multiply relapsed Hodgkin lymphoma (idea)
• ctDNA monitoring in lymphoma (PhasED-seq, clonoSEQ) (technology)
• PET-adapted (response-adapted) therapy (technology)
• CD30 (target)
• GHSG HD21 (trial)

• SWOG S1826 (phase 3, n=994): Progression-free survival at 2 years: 92% vs 83%, HR 0.45
• ECHELON-1 (phase 3, n=1,334): Modified PFS at 2 years: 82.1% vs 77.2%, HR 0.77
• RATHL (phase 3, n=1,214): Progression-free survival at 3 years (PET2-negative): 85.7% vs 84.4%
• GHSG HD21 (phase 3, n=1,500): Progression-free survival at 4 years: 94.3% vs 90.9%, HR 0.66
• AETHERA (phase 3, n=329): Progression-free survival (median): 42.9 months vs 24.1 months, HR 0.57
• KEYNOTE-204 (phase 3, n=304): Progression-free survival (median): 13.2 months vs 8.3 months, HR 0.65

• Late toxicity in survivors.
• Older patients.
• Late effects dominate: cardiac disease, breast and lung cancer after mediastinal radiotherapy, infertility; survivors need lifelong surveillance that most health systems do not organise.
• Older patients (>60) have roughly half the cure rate and double the toxicity; the best regimen for them is unsettled.
• The ~10-15% with primary refractory or early-relapsing disease still need transplant; those failing PD-1 blockade have few options beyond allogeneic transplant.
• Interim PET has limited positive predictive value; ctDNA-guided designs are unproven.

1. Which cooperative group ran the trial that put nivolumab into first-line Hodgkin lymphoma?
   Answer

   SWOG (S1826, nivolumab-AVD vs BV-AVD), leading to FDA approval in March 2026 for ages 12 and over.
2. What is the standard treatment for stage II-III triple-negative breast cancer today?
   Answer

   Neoadjuvant pembrolizumab with carboplatin/paclitaxel then anthracycline chemotherapy, surgery, and adjuvant pembrolizumab (KEYNOTE-522); adjuvant olaparib for germline BRCA carriers with residual disease (OlympiA); capecitabine for residual disease without BRCA.
3. What fraction of advanced melanoma patients on nivolumab plus ipilimumab are alive at ten years?
   Answer

   About 43% overall survival (CheckMate 067), with melanoma-specific survival around 52%.
4. What is the difference between a CT scan and a PET scan?
   Answer

   CT is a fast 3D X-ray showing size and shape; PET shows biology by tracking where a radioactive tracer accumulates (for example glucose uptake with FDG or a specific protein such as PSMA). PET/CT combines both.

• Wikipedia: https://en.wikipedia.org/wiki/Hodgkin_lymphoma
• Guideline: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1439