{"entity":{"id":"perseus","kind":"trial","name":"PERSEUS","aka":[],"tldr":"Adding daratumumab to the standard three-drug induction and to maintenance cut the risk of progression by more than half in transplant-eligible myeloma.","summary":"PERSEUS, trial NCT03710603 sponsored by the European Myeloma Network and Janssen and published in the New England Journal of Medicine in 2024, showed that adding daratumumab to bortezomib, lenalidomide and dexamethasone induction and to lenalidomide maintenance cut the risk of progression by more than half in transplant-eligible newly diagnosed myeloma. It randomised 709 patients, met its primary progression-free survival endpoint at 48 months with far higher and more sustained MRD negativity, and led to approval in July 2024, with daratumumab stopped after sustained MRD negativity in the experimental arm, embedding MRD-guided de-escalation. Whether transplant is still needed on top of a quadruplet is the open question.","status":"positive","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT03710603","url":"https://clinicaltrials.gov/study/NCT03710603"},{"label":"NEJM 2024","url":"https://www.nejm.org/doi/full/10.1056/NEJMoa2312054"}],"tags":[],"related":[],"cancers":["multiple-myeloma","myeloma-transplant-eligible"],"sections":[],"technologies":["autologous-stem-cell-transplant"],"targets":[],"drugs":["daratumumab","bortezomib","lenalidomide"],"companies":["johnson-johnson"],"institutions":[],"pathways":[],"terms":["mrd-negativity-myeloma"],"trials":[],"people":["pieter-sonneveld"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT03710603","phase":"3","setting":"Newly diagnosed transplant-eligible myeloma: Dara-VRd induction/consolidation + DR maintenance vs VRd + R","sponsor":"EMN / Janssen","result":"PFS HR 0.42; 48-month PFS 84.3% vs 67.7%.","started":"2018-12-14","startedType":"actual","yearReported":2023,"enrolled":709,"enrolledBasis":"registry","outcomes":[{"endpoint":"Progression-free survival at 48 months","primary":true,"unit":"%","arms":[{"name":"Dara-VRd","n":355,"value":84.3},{"name":"VRd","n":354,"value":67.7}],"hr":0.42,"ci":[0.3,0.59],"p":"<0.0001","source":"https://www.nejm.org/doi/full/10.1056/NEJMoa2312054"},{"endpoint":"MRD negativity (10⁻⁵)","unit":"%","arms":[{"name":"Dara-VRd","value":75.2},{"name":"VRd","value":47.5}],"source":"https://doi.org/10.1056/NEJMoa2312054"}],"replication":"Consistent with GRIFFIN (phase 2) and with CASSIOPEIA (Dara-VTd); Isa-VRd in IsKia and IMROZ show the same class effect."},"route":"/trials/perseus/","neighbours":{"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/"}],"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":"hovon","kind":"company","name":"HOVON","route":"/companies/hovon/"},{"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":"smart-design","kind":"term","name":"SMART design (sequential multiple assignment randomised trial)","route":"/terms/smart-design/"},{"id":"surrogate-validation","kind":"term","name":"Surrogate endpoint validation: which stand-ins have earned trust","route":"/terms/surrogate-validation/"}],"person":[{"id":"pieter-sonneveld","kind":"person","name":"Pieter Sonneveld","route":"/people/pieter-sonneveld/"}],"pairing":[{"id":"cd38-plus-triplet","kind":"pairing","name":"CD38 antibody added to PI-IMiD-dex (quadruplet induction)","route":"/pairings/cd38-plus-triplet/"}],"idea":[{"id":"idea-mrd-guided-stop-myeloma","kind":"idea","name":"MRD-guided treatment-free intervals in myeloma","route":"/ideas/idea-mrd-guided-stop-myeloma/"}],"paper":[{"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","route":"/key-papers/paper-perseus-dara-vrd-transplant-nejm-2024/"}]}}