{"entity":{"id":"paper-zuma-1-axi-cel-nejm-2017","kind":"paper","name":"ZUMA-1: axicabtagene ciloleucel for refractory large B-cell lymphoma, the first CAR-T approved for lymphoma","aka":[],"tldr":"In lymphoma refractory to chemotherapy, where expected survival was around six months, a single CAR-T infusion produced responses in 82% of patients and long-term remission in about 40%.","summary":"ZUMA-1 was a multicentre single-arm phase 2 trial of axicabtagene ciloleucel (axi-cel), a CD19 CAR-T with a CD28 costimulatory domain, in 111 enrolled and 101 treated patients with refractory diffuse large B-cell, primary mediastinal or transformed follicular lymphoma. Manufacturing succeeded in 99% and the median time from apheresis to delivery was 17 days. The objective response rate was 82% with complete response in 54%; at a median follow-up of 15.4 months 42% remained in response (40% in complete response), and 18-month overall survival was 52%. Grade 3 or higher cytokine release syndrome occurred in 13% and neurological events in 28%. Five-year follow-up showed overall survival of about 43% with a plateau, consistent with cure in a substantial minority. It supported FDA approval in October 2017.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1056/NEJMoa1707447"},{"label":"ClinicalTrials.gov NCT02348216","url":"https://clinicaltrials.gov/study/NCT02348216"}],"tags":[],"related":["paper-zuma-7-axi-cel-second-line-nejm-2022","paper-juliet-tisagenlecleucel-dlbcl-nejm-2019","lymphoma-roadmap","paper-transcend-nhl-001-liso-cel-lancet-2020"],"cancers":["dlbcl","follicular-lymphoma"],"sections":[],"technologies":["car-t"],"targets":["cd19"],"drugs":["axicabtagene-ciloleucel"],"companies":["gilead"],"institutions":["md-anderson","moffitt"],"pathways":[],"terms":["crs","icans","orr"],"trials":["zuma-7"],"people":["frederick-locke"],"bottlenecks":["b-manufacturing-cell-therapy","b-toxicity-qol"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2017,"doi":"10.1056/NEJMoa1707447","authors":"Neelapu SS, Locke FL, Bartlett NL, et al.","paperType":"translational","findings":["111 enrolled, 101 treated patients with chemotherapy-refractory large B-cell lymphoma; 22 centres.","Manufacturing success 99%; median 17 days from apheresis to delivery; no bridging chemotherapy allowed.","Objective response 82%; complete response 54%; 42% still responding at 15.4 months median follow-up.","18-month overall survival 52%; 5-year overall survival about 43% with a plateau.","Grade 3 or higher CRS 13%; grade 3 or higher neurological events 28%; 3 deaths during treatment."],"whatItMeans":"ZUMA-1 showed that CAR-T can cure a meaningful fraction of adults whose aggressive lymphoma no longer responds to chemotherapy, a group with a historical median survival of about six months (SCHOLAR-1). Axi-cel became the first CAR-T approved for lymphoma and later the first to beat standard second-line therapy in ZUMA-7. The comparatively high neurotoxicity of CD28-costimulated products was also first characterised here.","caveats":["Single-arm with a historical comparator (SCHOLAR-1).","No bridging therapy was allowed, selecting patients with slower-growing disease.","Roughly 60% of patients eventually relapsed or died; long-term survivors are a minority.","Toxicity required intensive-care-capable centres; real-world use has since expanded with prophylactic steroids."],"changedPractice":true,"participants":101},"route":"/key-papers/paper-zuma-1-axi-cel-nejm-2017/","neighbours":{"paper":[{"id":"paper-juliet-tisagenlecleucel-dlbcl-nejm-2019","kind":"paper","name":"JULIET: tisagenlecleucel for adults with relapsed or refractory diffuse large B-cell lymphoma","route":"/key-papers/paper-juliet-tisagenlecleucel-dlbcl-nejm-2019/"},{"id":"paper-transcend-nhl-001-liso-cel-lancet-2020","kind":"paper","name":"Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study","route":"/key-papers/paper-transcend-nhl-001-liso-cel-lancet-2020/"},{"id":"paper-zuma-2-brexu-cel-mantle-cell-nejm-2020","kind":"paper","name":"ZUMA-2: brexu-cel CAR-T for mantle cell lymphoma that has failed BTK inhibitors","route":"/key-papers/paper-zuma-2-brexu-cel-mantle-cell-nejm-2020/"},{"id":"paper-zuma-7-axi-cel-second-line-nejm-2022","kind":"paper","name":"ZUMA-7: axi-cel CAR-T instead of salvage chemotherapy and transplant for large B-cell lymphoma that relapses early","route":"/key-papers/paper-zuma-7-axi-cel-second-line-nejm-2022/"}],"roadmap":[{"id":"lymphoma-roadmap","kind":"roadmap","name":"Lymphoma roadmap: from a jaw tumour in Uganda and the first human cancer virus to gene-expression subtypes, PET-adapted chemotherapy, CAR-T cells, bispecific antibodies and the genetics-directed trials now recruiting","route":"/roadmaps/lymphoma-roadmap/"}],"cancer":[{"id":"dlbcl","kind":"cancer","name":"Diffuse large B-cell lymphoma","route":"/cancers/dlbcl/"},{"id":"follicular-lymphoma","kind":"cancer","name":"Follicular lymphoma","route":"/cancers/follicular-lymphoma/"}],"technology":[{"id":"car-t","kind":"technology","name":"CAR-T cell therapy","route":"/technologies/car-t/"}],"target":[{"id":"cd19","kind":"target","name":"CD19","route":"/targets/cd19/"}],"drug":[{"id":"axicabtagene-ciloleucel","kind":"drug","name":"Axicabtagene ciloleucel","route":"/drugs/axicabtagene-ciloleucel/"}],"company":[{"id":"gilead","kind":"company","name":"Gilead Sciences (incl. Kite)","route":"/companies/gilead/"}],"institution":[{"id":"md-anderson","kind":"institution","name":"MD Anderson Cancer Center","route":"/institutions/md-anderson/"},{"id":"moffitt","kind":"institution","name":"Moffitt Cancer Center","route":"/institutions/moffitt/"}],"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":"zuma-7","kind":"trial","name":"ZUMA-7","route":"/trials/zuma-7/"}],"person":[{"id":"frederick-locke","kind":"person","name":"Frederick L. Locke","route":"/people/frederick-locke/"},{"id":"michel-sadelain","kind":"person","name":"Michel Sadelain","route":"/people/michel-sadelain/"},{"id":"sattva-neelapu","kind":"person","name":"Sattva S. Neelapu","route":"/people/sattva-neelapu/"}],"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":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}],"idea":[{"id":"idea-bispecific-vs-car-t-second-line","kind":"idea","name":"Head-to-head bispecific vs CAR-T in second-line LBCL","route":"/ideas/idea-bispecific-vs-car-t-second-line/"}]}}