{"entity":{"id":"cartitude-4","kind":"trial","name":"CARTITUDE-4","aka":[],"tldr":"The first randomised trial to show a CAR-T improves survival in myeloma, as early as second line.","summary":"CARTITUDE-4, trial NCT04181827 sponsored by Janssen and Legend and published in the New England Journal of Medicine in 2023, was the first randomised trial to show that a CAR-T improves survival in myeloma, as early as the second line. It randomised 419 lenalidomide-refractory patients after one to three prior lines to ciltacabtagene autoleucel or standard combinations, met its primary progression-free survival endpoint with a very large effect, showed an overall survival benefit at ASCO 2024 and far higher MRD negativity, and led to approval for patients with at least one prior line in April 2024. Whether CAR-T should replace transplant in the frontline, which CARTITUDE-5 and CARTITUDE-6 test, is the open question.","status":"positive","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT04181827","url":"https://clinicaltrials.gov/study/NCT04181827"}],"tags":[],"related":[],"cancers":["multiple-myeloma","myeloma-relapsed-refractory"],"sections":[],"technologies":["car-t"],"targets":[],"drugs":["ciltacabtagene-autoleucel"],"companies":["johnson-johnson","legend-biotech"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["jesus-san-miguel"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT04181827","phase":"3","setting":"Lenalidomide-refractory myeloma after 1-3 prior lines: cilta-cel vs Pom-Vd or Dara-Pd","sponsor":"Janssen / Legend","result":"PFS HR 0.26; OS HR 0.55.","started":"2020-06-12","startedType":"actual","yearReported":2023,"enrolled":419,"enrolledBasis":"registry","outcomes":[{"endpoint":"Progression-free survival","primary":true,"arms":[{"name":"Cilta-cel","n":208},{"name":"Standard care","n":211}],"hr":0.26,"ci":[0.18,0.38],"p":"<0.001","source":"https://www.nejm.org/doi/full/10.1056/NEJMoa2303379"},{"endpoint":"Overall survival","arms":[{"name":"Cilta-cel"},{"name":"Standard care"}],"hr":0.55,"ci":[0.39,0.79],"source":"https://doi.org/10.1056/NEJMoa2303379"}],"replication":"KarMMa-3 (ide-cel) showed a PFS benefit of similar direction but smaller size (HR 0.49) without a clear OS benefit."},"route":"/trials/cartitude-4/","neighbours":{"cancer":[{"id":"multiple-myeloma","kind":"cancer","name":"Multiple myeloma","route":"/cancers/multiple-myeloma/"},{"id":"myeloma-relapsed-refractory","kind":"cancer","name":"Relapsed or refractory multiple myeloma","route":"/cancers/myeloma-relapsed-refractory/"}],"technology":[{"id":"car-t","kind":"technology","name":"CAR-T cell therapy","route":"/technologies/car-t/"}],"drug":[{"id":"ciltacabtagene-autoleucel","kind":"drug","name":"Ciltacabtagene autoleucel","route":"/drugs/ciltacabtagene-autoleucel/"}],"company":[{"id":"johnson-johnson","kind":"company","name":"Johnson & Johnson","route":"/companies/johnson-johnson/"},{"id":"legend-biotech","kind":"company","name":"Legend Biotech","route":"/companies/legend-biotech/"}],"person":[{"id":"jesus-san-miguel","kind":"person","name":"Jesús San Miguel","route":"/people/jesus-san-miguel/"}],"idea":[{"id":"idea-fund-public-car-t-manufacturing","kind":"idea","name":"Hospital-based CAR-T manufacturing at cost through a public network","route":"/ideas/idea-fund-public-car-t-manufacturing/"},{"id":"idea-reg-point-of-care-cart-network","kind":"idea","name":"Hospital-made CAR-T under one shared regulatory master file","route":"/ideas/idea-reg-point-of-care-cart-network/"},{"id":"idea-car-t-replaces-transplant","kind":"idea","name":"One CAR-T infusion instead of autologous transplant","route":"/ideas/idea-car-t-replaces-transplant/"}],"bottleneck":[{"id":"b-manufacturing-cell-therapy","kind":"bottleneck","name":"Manufacturing cost and time for living and radioactive medicines","route":"/bottlenecks/b-manufacturing-cell-therapy/"}],"paper":[{"id":"paper-cartitude-4-cilta-cel-nejm-2023","kind":"paper","name":"CARTITUDE-4: cilta-cel CAR-T versus standard combinations after one to three prior lines of myeloma therapy","route":"/key-papers/paper-cartitude-4-cilta-cel-nejm-2023/"}],"term":[{"id":"autologous-transplant","kind":"term","name":"Autologous stem cell transplant (ASCT)","route":"/terms/autologous-transplant/"},{"id":"vrd","kind":"term","name":"VRd and Dara-VRd (myeloma induction regimens)","route":"/terms/vrd/"}],"trial":[{"id":"legend-2","kind":"trial","name":"LEGEND-2","route":"/trials/legend-2/"}]}}