{"entity":{"id":"paper-perseus-dara-vrd-transplant-nejm-2024","kind":"paper","name":"PERSEUS: daratumumab added to bortezomib-lenalidomide-dexamethasone around autologous transplant in newly diagnosed myeloma","aka":[],"tldr":"Adding daratumumab to the standard three-drug induction, transplant and maintenance cut progression or death by 58% and pushed MRD-negativity to three-quarters of patients.","summary":"PERSEUS randomised 709 transplant-eligible patients with newly diagnosed multiple myeloma to daratumumab plus bortezomib, lenalidomide and dexamethasone (D-VRd) induction and consolidation with daratumumab-lenalidomide maintenance, or VRd with lenalidomide maintenance. The primary endpoint was PFS. At 48 months PFS was 84.3% versus 67.7% (hazard ratio 0.42); complete response or better was 87.9% versus 70.1% and MRD-negativity at 10^-5 was 75.2% versus 47.5%. Daratumumab could be stopped after two years of maintenance in patients with sustained MRD-negativity. Grade 3-4 neutropenia, thrombocytopenia and infections were more frequent with daratumumab.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1056/NEJMoa2312054"},{"label":"ClinicalTrials.gov NCT03710603","url":"https://clinicaltrials.gov/study/NCT03710603"}],"tags":[],"related":["cd38-plus-triplet"],"cancers":["multiple-myeloma"],"sections":[],"technologies":["autologous-stem-cell-transplant","mrd-testing"],"targets":["cd38"],"drugs":["daratumumab","bortezomib","lenalidomide"],"companies":["johnson-johnson"],"institutions":[],"pathways":[],"terms":["pfs","mrd-negativity-myeloma"],"trials":["perseus"],"people":[],"bottlenecks":["b-dormancy-mrd","b-trial-design"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2024,"doi":"10.1056/NEJMoa2312054","authors":"Sonneveld P, Dimopoulos MA, Boccadoro M, et al.","paperType":"rct","findings":["709 transplant-eligible patients; D-VRd + D-R maintenance vs VRd + R maintenance.","48-month PFS 84.3% vs 67.7%; hazard ratio 0.42.","Complete response or better 87.9% vs 70.1%.","MRD-negativity (10^-5) 75.2% vs 47.5%; sustained MRD-negativity over 12 months 64.8% vs 29.7%.","More grade 3-4 neutropenia (62.1% vs 51.0%) and infections with daratumumab."],"whatItMeans":"PERSEUS, with the earlier GRIFFIN and CASSIOPEIA trials, made a four-drug daratumumab quadruplet the standard for fit patients heading to transplant. It also introduced MRD-directed stopping of the antibody, a step towards treatment that is deep but not indefinite. Whether transplant itself remains necessary on top of a quadruplet is now the open question.","caveats":["PFS, not overall survival, was the primary endpoint; OS follow-up is immature.","Both arms had autologous transplant, so it does not test transplant versus no transplant.","MRD-guided discontinuation applied only to daratumumab, not lenalidomide.","Younger, fitter patients than typical clinic populations."],"changedPractice":true,"participants":709},"route":"/key-papers/paper-perseus-dara-vrd-transplant-nejm-2024/","neighbours":{"pairing":[{"id":"cd38-plus-triplet","kind":"pairing","name":"CD38 antibody added to PI-IMiD-dex (quadruplet induction)","route":"/pairings/cd38-plus-triplet/"}],"cancer":[{"id":"multiple-myeloma","kind":"cancer","name":"Multiple myeloma","route":"/cancers/multiple-myeloma/"},{"id":"myeloma-transplant-eligible","kind":"cancer","name":"Newly diagnosed multiple myeloma, transplant-eligible","route":"/cancers/myeloma-transplant-eligible/"}],"technology":[{"id":"autologous-stem-cell-transplant","kind":"technology","name":"Autologous stem cell transplant (high-dose therapy)","route":"/technologies/autologous-stem-cell-transplant/"},{"id":"mrd-testing","kind":"technology","name":"MRD / molecular residual disease testing","route":"/technologies/mrd-testing/"}],"target":[{"id":"cd38","kind":"target","name":"CD38","route":"/targets/cd38/"}],"drug":[{"id":"bortezomib","kind":"drug","name":"Bortezomib","route":"/drugs/bortezomib/"},{"id":"daratumumab","kind":"drug","name":"Daratumumab","route":"/drugs/daratumumab/"},{"id":"lenalidomide","kind":"drug","name":"Lenalidomide","route":"/drugs/lenalidomide/"}],"company":[{"id":"johnson-johnson","kind":"company","name":"Johnson & Johnson","route":"/companies/johnson-johnson/"}],"term":[{"id":"mrd-negativity-myeloma","kind":"term","name":"MRD negativity (myeloma, 10⁻⁵ / 10⁻⁶)","route":"/terms/mrd-negativity-myeloma/"},{"id":"pfs","kind":"term","name":"Progression-free survival (PFS)","route":"/terms/pfs/"}],"trial":[{"id":"perseus","kind":"trial","name":"PERSEUS","route":"/trials/perseus/"}],"bottleneck":[{"id":"b-dormancy-mrd","kind":"bottleneck","name":"Dormant cells and minimal residual disease","route":"/bottlenecks/b-dormancy-mrd/"},{"id":"b-trial-design","kind":"bottleneck","name":"Trial design, endpoints and cost","route":"/bottlenecks/b-trial-design/"}],"journal":[{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}],"person":[{"id":"pieter-sonneveld","kind":"person","name":"Pieter Sonneveld","route":"/people/pieter-sonneveld/"}]}}