{"entity":{"id":"paper-eliana-tisagenlecleucel-nejm-2018","kind":"paper","name":"ELIANA: the global trial that made tisagenlecleucel the first approved CAR-T therapy for children and young adults with relapsed ALL","aka":[],"tldr":"Across 25 centres, 81% of children and young adults with relapsed or refractory ALL went into remission after a single tisagenlecleucel infusion, and half were still event-free a year later.","summary":"ELIANA was a single-arm, multicentre phase 2 trial of tisagenlecleucel in patients aged 3-21 with CD19-positive relapsed or refractory B-cell ALL. Of 92 enrolled, 75 received an infusion; the rest could not because of manufacturing failure, death or adverse events. The overall remission rate within three months was 81%, all MRD-negative; event-free survival was 73% at six months and 50% at 12 months, with overall survival 90% and 76%. Cytokine release syndrome occurred in 77% (grade 3-4 in about 46%) and neurological events in 40%. The trial supported FDA approval in August 2017, the first gene therapy and first CAR-T approved in the United States, and demonstrated that a centrally manufactured autologous cell product could be delivered across continents.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1056/NEJMoa1709866"},{"label":"ClinicalTrials.gov NCT02435849","url":"https://clinicaltrials.gov/study/NCT02435849"}],"tags":[],"related":["paper-maude-ctl019-all-nejm-2014","apheresis-starting-material"],"cancers":["all-leukemia","all-paediatric-relapsed"],"sections":[],"technologies":["car-t"],"targets":["cd19"],"drugs":["tisagenlecleucel","obecabtagene-autoleucel"],"companies":["novartis"],"institutions":["penn-abramson"],"pathways":[],"terms":["crs","icans","efs"],"trials":["eliana"],"people":["carl-june","bruce-levine"],"bottlenecks":["b-manufacturing-cell-therapy","b-drug-pricing","b-global-access"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2018,"doi":"10.1056/NEJMoa1709866","authors":"Maude SL, Laetsch TW, Buechner J, et al.","paperType":"translational","findings":["92 enrolled, 75 infused; 25 centres in 11 countries; median age 11.","Overall remission rate within 3 months 81%; all remissions MRD-negative.","Event-free survival 73% at 6 months and 50% at 12 months; overall survival 90% and 76%.","CRS 77% (grade 3-4 in about 46%; 48% needed tocilizumab; 47% intensive care); neurological events 40%.","Manufacturing failed in 7 of 92 and 17 enrolled patients were never infused, highlighting the vein-to-vein problem."],"whatItMeans":"ELIANA turned CAR-T from a single-centre experiment into a licensed product and created the regulatory and logistical template every later cell therapy has followed. For children with refractory leukaemia it offers a chance of durable remission without transplant. The trial also exposed the gaps: manufacturing failures, patients dying while waiting, and roughly half relapsing within a few years.","caveats":["Single-arm; no randomised comparator and outcomes reported on infused rather than enrolled patients in most analyses.","Severe CRS rates were high by later standards, before prophylactic strategies.","Long-term relapse, often CD19-negative, affects about half; some patients still proceed to transplant.","List price around 475,000 US dollars at launch raised affordability and access questions."],"changedPractice":true,"participants":75},"route":"/key-papers/paper-eliana-tisagenlecleucel-nejm-2018/","neighbours":{"paper":[{"id":"paper-maude-ctl019-all-nejm-2014","kind":"paper","name":"Maude 2014: CD19 CAR-T cells produce complete remission in 27 of 30 children and adults with relapsed ALL","route":"/key-papers/paper-maude-ctl019-all-nejm-2014/"},{"id":"paper-ucart19-allogeneic-car-t-lancet-2020","kind":"paper","name":"UCART19: the first gene-edited, donor-derived CAR-T cells in children and adults with relapsed B-cell ALL","route":"/key-papers/paper-ucart19-allogeneic-car-t-lancet-2020/"}],"technology":[{"id":"apheresis-starting-material","kind":"technology","name":"Apheresis and starting-material collection","route":"/technologies/apheresis-starting-material/"},{"id":"car-t","kind":"technology","name":"CAR-T cell therapy","route":"/technologies/car-t/"}],"cancer":[{"id":"all-leukemia","kind":"cancer","name":"Acute lymphoblastic leukaemia","route":"/cancers/all-leukemia/"},{"id":"all-paediatric-relapsed","kind":"cancer","name":"Relapsed and refractory acute lymphoblastic leukaemia in children","route":"/cancers/all-paediatric-relapsed/"}],"target":[{"id":"cd19","kind":"target","name":"CD19","route":"/targets/cd19/"}],"drug":[{"id":"obecabtagene-autoleucel","kind":"drug","name":"Obecabtagene autoleucel","route":"/drugs/obecabtagene-autoleucel/"},{"id":"tisagenlecleucel","kind":"drug","name":"Tisagenlecleucel","route":"/drugs/tisagenlecleucel/"}],"company":[{"id":"novartis","kind":"company","name":"Novartis","route":"/companies/novartis/"}],"institution":[{"id":"penn-abramson","kind":"institution","name":"Abramson Cancer Center, University of Pennsylvania","route":"/institutions/penn-abramson/"}],"term":[{"id":"crs","kind":"term","name":"Cytokine release syndrome (CRS)","route":"/terms/crs/"},{"id":"efs","kind":"term","name":"Event-free / disease-free survival (EFS, DFS, iDFS, RFS)","route":"/terms/efs/"},{"id":"icans","kind":"term","name":"ICANS (neurotoxicity)","route":"/terms/icans/"}],"trial":[{"id":"eliana","kind":"trial","name":"ELIANA","route":"/trials/eliana/"}],"person":[{"id":"bruce-levine","kind":"person","name":"Bruce L. Levine","route":"/people/bruce-levine/"},{"id":"carl-june","kind":"person","name":"Carl H. June","route":"/people/carl-june/"},{"id":"stephan-grupp","kind":"person","name":"Stephan A. Grupp","route":"/people/stephan-grupp/"}],"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/"},{"id":"b-drug-pricing","kind":"bottleneck","name":"Prices and value","route":"/bottlenecks/b-drug-pricing/"}],"journal":[{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}]}}