{"entity":{"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","aka":[],"tldr":"Moving BCMA CAR-T to the second line cut the risk of progression or death by 74% compared with standard triplets, and later improved overall survival.","summary":"CARTITUDE-4 randomised 419 patients with lenalidomide-refractory multiple myeloma after one to three prior lines to a single infusion of ciltacabtagene autoleucel (after bridging therapy) or standard of care (pomalidomide-bortezomib-dexamethasone or daratumumab-pomalidomide-dexamethasone). The primary endpoint was PFS by intention to treat. At 12 months PFS was 75.9% versus 48.6% (hazard ratio 0.26); overall response was 84.6% versus 67.3%, complete response or better 73.1% versus 21.8%, and MRD-negativity 60.6% versus 15.6%. In later follow-up overall survival was significantly better with cilta-cel (hazard ratio about 0.55). Toxicity was manageable, with lower CRS and neurotoxicity rates than in CARTITUDE-1.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1056/NEJMoa2303379"},{"label":"ClinicalTrials.gov NCT04181827","url":"https://clinicaltrials.gov/study/NCT04181827"}],"tags":[],"related":["paper-karmma-3-ide-cel-nejm-2023"],"cancers":["multiple-myeloma"],"sections":[],"technologies":["car-t"],"targets":["bcma"],"drugs":["ciltacabtagene-autoleucel","daratumumab","pomalidomide","bortezomib"],"companies":["legend-biotech","johnson-johnson"],"institutions":[],"pathways":[],"terms":["pfs","os","mrd-negativity-myeloma","crs"],"trials":["cartitude-4","cartitude-5"],"people":[],"bottlenecks":["b-manufacturing-cell-therapy","b-global-access"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2023,"doi":"10.1056/NEJMoa2303379","authors":"San-Miguel J, Dhakal B, Yong K, et al.","paperType":"rct","findings":["419 lenalidomide-refractory patients after 1-3 prior lines; cilta-cel vs PVd or DPd.","12-month PFS 75.9% vs 48.6%; hazard ratio 0.26 (intention-to-treat).","Complete response or better 73.1% vs 21.8%; MRD-negativity 60.6% vs 15.6%.","Overall survival significantly improved at second analysis (HR about 0.55).","CRS in 76% of infused patients (grade 3-4 about 1%); ICANS about 5%; cranial nerve palsy and movement disorders in a small minority."],"whatItMeans":"CARTITUDE-4 is the first randomised trial to show that a CAR-T improves survival in myeloma, and it moved cilta-cel into second-line use (FDA approval 2024). For patients whose disease returns after first-line lenalidomide, a one-off cell therapy now competes with continuous drug combinations. Capacity, cost and the need for bridging therapy still limit who actually receives it.","caveats":["Open-label; standard-of-care arm was a mix of two regimens, neither of which is the strongest available.","Intention-to-treat analysis includes patients who progressed during bridging; per-protocol PFS is even more favourable.","Only about 15% of standard-arm patients later received CAR-T, so the comparison is partly CAR-T now versus never.","Secondary haematological malignancies and late neurotoxicity remain concerns."],"changedPractice":true,"participants":419},"route":"/key-papers/paper-cartitude-4-cilta-cel-nejm-2023/","neighbours":{"paper":[{"id":"paper-cartitude-1-cilta-cel-lancet-2021","kind":"paper","name":"CARTITUDE-1: cilta-cel, a BCMA CAR-T, in heavily pretreated myeloma","route":"/key-papers/paper-cartitude-1-cilta-cel-lancet-2021/"},{"id":"paper-karmma-3-ide-cel-nejm-2023","kind":"paper","name":"KarMMa-3: ide-cel CAR-T versus standard regimens in triple-class-exposed relapsed myeloma","route":"/key-papers/paper-karmma-3-ide-cel-nejm-2023/"}],"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/"}],"target":[{"id":"bcma","kind":"target","name":"BCMA","route":"/targets/bcma/"}],"drug":[{"id":"bortezomib","kind":"drug","name":"Bortezomib","route":"/drugs/bortezomib/"},{"id":"ciltacabtagene-autoleucel","kind":"drug","name":"Ciltacabtagene autoleucel","route":"/drugs/ciltacabtagene-autoleucel/"},{"id":"daratumumab","kind":"drug","name":"Daratumumab","route":"/drugs/daratumumab/"},{"id":"pomalidomide","kind":"drug","name":"Pomalidomide","route":"/drugs/pomalidomide/"}],"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/"}],"term":[{"id":"crs","kind":"term","name":"Cytokine release syndrome (CRS)","route":"/terms/crs/"},{"id":"mrd-negativity-myeloma","kind":"term","name":"MRD negativity (myeloma, 10⁻⁵ / 10⁻⁶)","route":"/terms/mrd-negativity-myeloma/"},{"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":"cartitude-4","kind":"trial","name":"CARTITUDE-4","route":"/trials/cartitude-4/"},{"id":"cartitude-5","kind":"trial","name":"CARTITUDE-5","route":"/trials/cartitude-5/"}],"bottleneck":[{"id":"b-manufacturing-cell-therapy","kind":"bottleneck","name":"Manufacturing cost and time for living and radioactive medicines","route":"/bottlenecks/b-manufacturing-cell-therapy/"},{"id":"b-global-access","kind":"bottleneck","name":"Most of the world has almost no cancer care","route":"/bottlenecks/b-global-access/"}],"journal":[{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}]}}