{"entity":{"id":"paper-echelon-3-brentuximab-lenalidomide-rituximab-dlbcl-jco-2025","kind":"paper","name":"Brentuximab vedotin combination for relapsed diffuse large B-cell lymphoma","aka":["ECHELON-3","Bartlett 2025"],"tldr":"Adding a CD30-directed antibody-drug conjugate to a tablet-and-antibody pairing added about five months of median survival for heavily pretreated people with relapsed aggressive lymphoma.","summary":"A randomised, double-blind, placebo-controlled, multicentre phase 3 trial comparing brentuximab vedotin with lenalidomide and rituximab against placebo with lenalidomide and rituximab in patients with relapsed or refractory diffuse large B-cell lymphoma. 230 patients were randomised, 112 to brentuximab vedotin and 118 to placebo; two in the placebo arm did not receive treatment. Brentuximab vedotin or placebo was given every three weeks, lenalidomide daily and rituximab every three weeks. Overall survival was the primary endpoint, with a prespecified interim analysis after 134 deaths against an efficacy boundary of two-sided p = 0.0232.\n\nAt a median follow-up of 16.4 months, median overall survival was 13.8 months with brentuximab vedotin against 8.5 months with placebo (hazard ratio 0.63, 95 per cent confidence interval 0.45 to 0.89, two-sided p = 0.009). Median progression-free survival was 4.2 months against 2.6 (hazard ratio 0.53, 0.38 to 0.73).","asOf":"2026-10-01","links":[{"label":"Journal of Clinical Oncology 2025","url":"https://doi.org/10.1200/JCO-24-02242"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39772655/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/39772655"}],"tags":["lymphoma-evidence"],"related":["lymphoma-roadmap"],"cancers":["dlbcl","non-hodgkin-lymphoma"],"sections":["adcs","immunotherapy"],"technologies":["adc"],"targets":["cd30","cd20"],"drugs":["brentuximab-vedotin","lenalidomide","rituximab"],"companies":["pfizer"],"institutions":[],"pathways":[],"terms":[],"trials":["nct04404283"],"people":[],"bottlenecks":["b-toxicity-qol","b-aging-comorbidity"],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2025,"doi":"10.1200/JCO-24-02242","pmid":"39772655","authors":"Bartlett NL, Hahn U, Kim WS, et al.","paperType":"rct","findings":["Median overall survival was 13.8 months with brentuximab vedotin, lenalidomide and rituximab against 8.5 months with placebo, lenalidomide and rituximab (hazard ratio 0.63, 95 per cent confidence interval 0.45 to 0.89, two-sided p = 0.009).","Median progression-free survival was 4.2 months against 2.6 months (hazard ratio 0.53, 0.38 to 0.73).","The result comes from a prespecified interim analysis after 134 overall survival events, against an efficacy boundary of two-sided p = 0.0232.","The trial was double-blind and placebo-controlled, which is unusual in this heavily pretreated setting."],"whatItMeans":"The evidence behind the United States approval of brentuximab vedotin with lenalidomide and a rituximab product for relapsed or refractory diffuse large B-cell lymphoma after two or more lines in patients not eligible for an autologous transplant or CAR-T. It is also the first demonstration that a CD30-directed conjugate helps in a disease where CD30 expression is variable.","caveats":["An interim analysis at a median follow-up of 16.4 months; the final overall survival estimate may move.","The comparator, lenalidomide with rituximab, is not a universal standard in this setting, so the size of the benefit against other options is unknown.","Medians of 13.8 and 8.5 months describe a population in which few are cured."],"changedPractice":true,"participants":230},"route":"/key-papers/paper-echelon-3-brentuximab-lenalidomide-rituximab-dlbcl-jco-2025/","neighbours":{"roadmap":[{"id":"lymphoma-roadmap","kind":"roadmap","name":"Lymphoma roadmap: from a jaw tumour in Uganda and the first human cancer virus to gene-expression subtypes, PET-adapted chemotherapy, CAR-T cells, bispecific antibodies and the genetics-directed trials now recruiting","route":"/roadmaps/lymphoma-roadmap/"}],"cancer":[{"id":"dlbcl","kind":"cancer","name":"Diffuse large B-cell lymphoma","route":"/cancers/dlbcl/"},{"id":"non-hodgkin-lymphoma","kind":"cancer","name":"Non-Hodgkin lymphoma (all types)","route":"/cancers/non-hodgkin-lymphoma/"}],"section":[{"id":"adcs","kind":"section","name":"Antibody-Drug Conjugates","route":"/fronts/adcs/"},{"id":"immunotherapy","kind":"section","name":"Immunotherapy","route":"/fronts/immunotherapy/"}],"technology":[{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"}],"target":[{"id":"cd20","kind":"target","name":"CD20","route":"/targets/cd20/"},{"id":"cd30","kind":"target","name":"CD30","route":"/targets/cd30/"}],"drug":[{"id":"brentuximab-vedotin","kind":"drug","name":"Brentuximab vedotin","route":"/drugs/brentuximab-vedotin/"},{"id":"lenalidomide","kind":"drug","name":"Lenalidomide","route":"/drugs/lenalidomide/"},{"id":"rituximab","kind":"drug","name":"Rituximab","route":"/drugs/rituximab/"}],"company":[{"id":"pfizer","kind":"company","name":"Pfizer (incl. Seagen)","route":"/companies/pfizer/"}],"trial":[{"id":"nct04404283","kind":"trial","name":"Brentuximab Vedotin Plus Lenalidomide and Rituximab for the Treatment of Relapsed/Refractory DLBCL","route":"/trials/nct04404283/"}],"bottleneck":[{"id":"b-aging-comorbidity","kind":"bottleneck","name":"Older and multimorbid patients are excluded and undertreated","route":"/bottlenecks/b-aging-comorbidity/"},{"id":"b-toxicity-qol","kind":"bottleneck","name":"Toxicity and quality of life are undervalued","route":"/bottlenecks/b-toxicity-qol/"}],"journal":[{"id":"jco","kind":"journal","name":"Journal of Clinical Oncology","route":"/journals/jco/"}]}}