# ECHELON-1: brentuximab vedotin replacing bleomycin in first-line chemotherapy for advanced Hodgkin lymphoma

Source: https://onco.cc/key-papers/paper-echelon-1-brentuximab-avd-nejm-2018/  
OnCo record `paper-echelon-1-brentuximab-avd-nejm-2018` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Swapping bleomycin for the CD30 antibody-drug conjugate brentuximab vedotin modestly improved disease control in advanced Hodgkin lymphoma and, at six years, improved survival.

## Summary

ECHELON-1 randomised 1334 patients with previously untreated stage III or IV classical Hodgkin lymphoma to brentuximab vedotin plus doxorubicin, vinblastine and dacarbazine (A+AVD) or standard ABVD for six cycles. The primary endpoint was modified PFS by independent review. At two years modified PFS was 82.1% versus 77.2% (hazard ratio 0.77). A+AVD caused more peripheral neuropathy (67% versus 43%) and febrile neutropenia (19% versus 8%) but eliminated bleomycin lung toxicity. The six-year update (Ansell et al., NEJM 2022) showed an overall survival benefit: 93.9% versus 89.4% (hazard ratio 0.59), the first OS improvement in front-line advanced Hodgkin lymphoma.

## Fields

- Kind: Key paper
- Last checked: 2026-09-08
- Journal: New England Journal of Medicine
- Year: 2018
- DOI: 10.1056/NEJMoa1708984
- Authors: Connors JM, Jurczak W, Straus DJ, et al.
- Findings: 1334 patients with stage III-IV classical Hodgkin lymphoma; A+AVD vs ABVD.; 2-year modified PFS 82.1% vs 77.2%; hazard ratio 0.77.; Peripheral neuropathy 67% vs 43%; febrile neutropenia 19% vs 8%; pulmonary toxicity lower with A+AVD.; 6-year overall survival 93.9% vs 89.4%; hazard ratio 0.59.; Fewer second malignancies and fewer patients needing subsequent therapy with A+AVD.
- What it means: 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.
- Caveats: Modified PFS was a novel composite endpoint counting incomplete response followed by further therapy as an event.; Early absolute benefit was small (about 5 points) and OS emerged only with long follow-up.; Excluded early-stage disease; older patients (over 60) had high toxicity with A+AVD.; Cost of brentuximab restricts use in lower-income settings.

## Sources

- Full text (DOI): https://doi.org/10.1056/NEJMoa1708984
- 6-year overall survival (Ansell 2022): https://doi.org/10.1056/NEJMoa2206125
- ClinicalTrials.gov NCT01712490: https://clinicaltrials.gov/study/NCT01712490

## Connected records

- key papers: [SWOG S1826: nivolumab plus AVD chemotherapy versus brentuximab-AVD for advanced Hodgkin lymphoma in adolescents and adults](https://onco.cc/key-papers/paper-swog-s1826-nivolumab-avd-nejm-2024/)
- cancers: [Advanced-stage classical Hodgkin lymphoma (stage III to IV)](https://onco.cc/cancers/advanced-stage-classical-hodgkin-lymphoma/), [Early-stage classical Hodgkin lymphoma (stage I to II)](https://onco.cc/cancers/early-stage-classical-hodgkin-lymphoma/), [Hodgkin lymphoma](https://onco.cc/cancers/hodgkin-lymphoma/)
- technologies: [Antibody-drug conjugate (ADC)](https://onco.cc/technologies/adc/)
- targets: [CD30](https://onco.cc/targets/cd30/)
- drugs: [Brentuximab vedotin](https://onco.cc/drugs/brentuximab-vedotin/), [Doxorubicin](https://onco.cc/drugs/doxorubicin/)
- companies: [Pfizer (incl. Seagen)](https://onco.cc/companies/pfizer/), [Takeda](https://onco.cc/companies/takeda/)
- terms: [Overall survival (OS)](https://onco.cc/terms/os/), [Progression-free survival (PFS)](https://onco.cc/terms/pfs/)
- trials: [ECHELON-1](https://onco.cc/trials/echelon-1/), [GHSG HD21](https://onco.cc/trials/hd21/), [SWOG S1826](https://onco.cc/trials/swog-s1826/)
- bottlenecks: [Survivorship and late effects are neglected](https://onco.cc/bottlenecks/b-survivorship/), [Toxicity and quality of life are undervalued](https://onco.cc/bottlenecks/b-toxicity-qol/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)
- people: [Joseph M. Connors](https://onco.cc/people/joseph-connors/)

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