Classic Hodgkin Lymphoma (cHL)

Evidence-based treatment sequencing for classic Hodgkin lymphoma, integrating stage/risk stratification to guide frontline brentuximab vedotin + AVD (ECHELON-1) versus ABVD, with salvage chemotherapy plus autologous transplant and checkpoint-inhibitor / brentuximab therapy for relapsed/refractory disease.

Frontline selection by stage and risk (Ann Arbor stage, IPS)

• Advanced-stage frontline standard → Brentuximab vedotin + AVD (BV-AVD)
• Early-stage or selected cohort → ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine)

1L: Brentuximab vedotin + AVD (BV-AVD)

Modern category-1 frontline standard for advanced-stage cHL, replacing bleomycin with the anti-CD30 ADC to reduce pulmonary toxicity and improve progression-free (and overall) survival (ECHELON-1). Requires G-CSF support and peripheral-neuropathy monitoring.

• Relapse or refractory disease → Relapsed or refractory disease — transplant eligibility assessment

1L: ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine)

Established frontline standard for early-stage disease (often with involved-site radiotherapy) and a selected advanced-stage alternative; PET-adapted bleomycin omission after cycle 2 mitigates pulmonary toxicity. Monitor pulmonary function on bleomycin.

• Relapse or refractory disease → Relapsed or refractory disease — transplant eligibility assessment

Relapsed or refractory disease — transplant eligibility assessment

• Transplant-eligible relapse → Salvage chemotherapy (ICE / GVD) + autologous stem cell transplant
• Transplant-ineligible or post-transplant relapse → Checkpoint inhibitor (nivolumab / pembrolizumab) or brentuximab vedotin

2L: Salvage chemotherapy (ICE / GVD) + autologous stem cell transplant

For transplant-eligible relapse: second-line salvage chemotherapy to achieve chemosensitive response (ideally PET-negative) followed by high-dose therapy and autologous stem cell transplant. Brentuximab vedotin consolidation/maintenance is used post-ASCT in high-risk patients (AETHERA).

• Subsequent progression → Clinical trial / allogeneic transplant / supportive care

2L: Checkpoint inhibitor (nivolumab / pembrolizumab) or brentuximab vedotin

For transplant-ineligible second-line relapse: PD-1 blockade (nivolumab or pembrolizumab, exploiting 9p24.1/PD-L1 amplification in cHL) or brentuximab vedotin. In multiply relapsed or post-ASCT disease these agents are used at later lines, often as a bridge to allogeneic transplant or clinical trial (see next step).

• Subsequent progression → Clinical trial / allogeneic transplant / supportive care

3L+: Clinical trial / allogeneic transplant / supportive care

For multiply relapsed disease, evaluate allogeneic stem cell transplantation and prioritize clinical-trial enrollment; supportive/palliative care as appropriate.