{"entity":{"id":"paper-cartitude-1-cilta-cel-lancet-2021","kind":"paper","name":"CARTITUDE-1: cilta-cel, a BCMA CAR-T, in heavily pretreated myeloma","aka":[],"tldr":"A single infusion of BCMA-directed CAR-T cells produced responses in 97% of patients whose myeloma had failed a median of six prior lines, with two-thirds reaching stringent complete response.","summary":"CARTITUDE-1 was a phase 1b/2 single-arm study of ciltacabtagene autoleucel (cilta-cel), a CAR-T with two BCMA-binding domains, in 97 patients with relapsed or refractory multiple myeloma exposed to a proteasome inhibitor, an immunomodulatory drug and an anti-CD38 antibody (median six prior lines, 88% triple-class refractory). The overall response rate was 97%, with stringent complete response in 67%; 12-month PFS was 77% and OS 89%. Cytokine release syndrome occurred in 95% (grade 3-4 in about 4%) and neurotoxicity in about 21%, including a small number of delayed movement and neurocognitive events. Long-term follow-up showed roughly a third of patients progression-free at five years without further therapy, unprecedented in this population.","asOf":"2026-09-08","links":[{"label":"PubMed search","url":"https://pubmed.ncbi.nlm.nih.gov/?term=CARTITUDE-1%20ciltacabtagene%20autoleucel%20Berdeja%20Lancet%202021"},{"label":"ClinicalTrials.gov NCT03548207","url":"https://clinicaltrials.gov/study/NCT03548207"}],"tags":[],"related":["paper-cartitude-4-cilta-cel-nejm-2023"],"cancers":["multiple-myeloma"],"sections":[],"technologies":["car-t"],"targets":["bcma"],"drugs":["ciltacabtagene-autoleucel"],"companies":["legend-biotech","johnson-johnson"],"institutions":[],"pathways":[],"terms":["crs","icans","orr"],"trials":["cartitude-1"],"people":["saad-usmani"],"bottlenecks":["b-manufacturing-cell-therapy","b-toxicity-qol"],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2021,"doi":"10.1016/S0140-6736(21)00933-8","pmid":"34175021","authors":"Berdeja JG, Madduri D, Usmani SZ, et al.","paperType":"translational","findings":["97 patients infused; median 6 prior lines; 88% triple-class refractory.","Overall response 97%; stringent complete response 67%; MRD-negativity in most evaluable responders.","12-month PFS 77%, OS 89%; median PFS about 35 months in later follow-up; about a third progression-free at 5 years.","CRS in 95% (grade 3-4 about 4%); ICANS 17%; delayed movement/neurocognitive syndrome in a minority.","Median time to CRS onset was 7 days, later than with CD19 CAR-Ts, enabling outpatient monitoring strategies."],"whatItMeans":"CARTITUDE-1 showed that a single CAR-T infusion can put late-stage myeloma into deep, multi-year remission, leading to FDA approval of cilta-cel in 2022 for heavily pretreated disease. It set the efficacy bar for BCMA-directed therapy and motivated moving CAR-T earlier (CARTITUDE-4). Late neurological toxicity and secondary malignancies remain the safety questions.","caveats":["Single-arm trial in fit, selected patients; no randomised comparator.","Manufacturing failures and bridging deaths are not captured in infused-patient analyses.","Delayed parkinsonism-like neurotoxicity and rare second primary malignancies (including T-cell lymphoma) emerged with follow-up.","Access limited by manufacturing slots and cost."],"changedPractice":true,"participants":97},"route":"/key-papers/paper-cartitude-1-cilta-cel-lancet-2021/","neighbours":{"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/"}],"cancer":[{"id":"multiple-myeloma","kind":"cancer","name":"Multiple myeloma","route":"/cancers/multiple-myeloma/"}],"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":"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/"}],"term":[{"id":"crs","kind":"term","name":"Cytokine release syndrome (CRS)","route":"/terms/crs/"},{"id":"icans","kind":"term","name":"ICANS (neurotoxicity)","route":"/terms/icans/"},{"id":"orr","kind":"term","name":"Objective response rate (ORR)","route":"/terms/orr/"}],"trial":[{"id":"cartitude-1","kind":"trial","name":"CARTITUDE-1","route":"/trials/cartitude-1/"}],"person":[{"id":"jesus-berdeja","kind":"person","name":"Jesús G. Berdeja","route":"/people/jesus-berdeja/"},{"id":"saad-usmani","kind":"person","name":"Saad Z. Usmani","route":"/people/saad-usmani/"}],"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-toxicity-qol","kind":"bottleneck","name":"Toxicity and quality of life are undervalued","route":"/bottlenecks/b-toxicity-qol/"}],"journal":[{"id":"lancet","kind":"journal","name":"The Lancet","route":"/journals/lancet/"}]}}