{"entity":{"id":"paper-echelon-1-brentuximab-avd-nejm-2018","kind":"paper","name":"ECHELON-1: brentuximab vedotin replacing bleomycin in first-line chemotherapy for advanced Hodgkin lymphoma","aka":[],"tldr":"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.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1056/NEJMoa1708984"},{"label":"6-year overall survival (Ansell 2022)","url":"https://doi.org/10.1056/NEJMoa2206125"},{"label":"ClinicalTrials.gov NCT01712490","url":"https://clinicaltrials.gov/study/NCT01712490"}],"tags":[],"related":["paper-swog-s1826-nivolumab-avd-nejm-2024"],"cancers":["hodgkin-lymphoma"],"sections":[],"technologies":["adc"],"targets":["cd30"],"drugs":["brentuximab-vedotin","doxorubicin"],"companies":["pfizer","takeda"],"institutions":[],"pathways":[],"terms":["pfs","os"],"trials":["echelon-1","hd21","swog-s1826"],"people":[],"bottlenecks":["b-toxicity-qol","b-survivorship"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2018,"doi":"10.1056/NEJMoa1708984","authors":"Connors JM, Jurczak W, Straus DJ, et al.","paperType":"rct","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."],"whatItMeans":"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."],"changedPractice":true,"participants":1334},"route":"/key-papers/paper-echelon-1-brentuximab-avd-nejm-2018/","neighbours":{"paper":[{"id":"paper-swog-s1826-nivolumab-avd-nejm-2024","kind":"paper","name":"SWOG S1826: nivolumab plus AVD chemotherapy versus brentuximab-AVD for advanced Hodgkin lymphoma in adolescents and adults","route":"/key-papers/paper-swog-s1826-nivolumab-avd-nejm-2024/"}],"cancer":[{"id":"advanced-stage-classical-hodgkin-lymphoma","kind":"cancer","name":"Advanced-stage classical Hodgkin lymphoma (stage III to IV)","route":"/cancers/advanced-stage-classical-hodgkin-lymphoma/"},{"id":"early-stage-classical-hodgkin-lymphoma","kind":"cancer","name":"Early-stage classical Hodgkin lymphoma (stage I to II)","route":"/cancers/early-stage-classical-hodgkin-lymphoma/"},{"id":"hodgkin-lymphoma","kind":"cancer","name":"Hodgkin lymphoma","route":"/cancers/hodgkin-lymphoma/"}],"technology":[{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"}],"target":[{"id":"cd30","kind":"target","name":"CD30","route":"/targets/cd30/"}],"drug":[{"id":"brentuximab-vedotin","kind":"drug","name":"Brentuximab vedotin","route":"/drugs/brentuximab-vedotin/"},{"id":"doxorubicin","kind":"drug","name":"Doxorubicin","route":"/drugs/doxorubicin/"}],"company":[{"id":"pfizer","kind":"company","name":"Pfizer (incl. Seagen)","route":"/companies/pfizer/"},{"id":"takeda","kind":"company","name":"Takeda","route":"/companies/takeda/"}],"term":[{"id":"os","kind":"term","name":"Overall survival (OS)","route":"/terms/os/"},{"id":"pfs","kind":"term","name":"Progression-free survival (PFS)","route":"/terms/pfs/"}],"trial":[{"id":"echelon-1","kind":"trial","name":"ECHELON-1","route":"/trials/echelon-1/"},{"id":"hd21","kind":"trial","name":"GHSG HD21","route":"/trials/hd21/"},{"id":"swog-s1826","kind":"trial","name":"SWOG S1826","route":"/trials/swog-s1826/"}],"bottleneck":[{"id":"b-survivorship","kind":"bottleneck","name":"Survivorship and late effects are neglected","route":"/bottlenecks/b-survivorship/"},{"id":"b-toxicity-qol","kind":"bottleneck","name":"Toxicity and quality of life are undervalued","route":"/bottlenecks/b-toxicity-qol/"}],"journal":[{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}],"person":[{"id":"joseph-connors","kind":"person","name":"Joseph M. Connors","route":"/people/joseph-connors/"}]}}