{"entity":{"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","aka":[],"tldr":"The first sizeable series of CD19 CAR-T therapy showed complete remission in 90% of patients with leukaemia that had failed everything else, with persistent engineered cells and a new, treatable toxicity.","summary":"Maude and colleagues reported 30 patients (25 children and 5 adults) with relapsed or refractory ALL, including 18 who had relapsed after allogeneic transplant and 3 refractory to blinatumomab, treated with CTL019, an autologous CD19-directed CAR-T with a 4-1BB costimulatory domain. Complete remission occurred in 27 (90%), including MRD-negative remissions; six-month event-free survival was 67% and overall survival 78%. CAR-T cells persisted for up to two years with ongoing B-cell aplasia. All patients developed cytokine release syndrome, severe in 27%, which was reversed by the IL-6 receptor antibody tocilizumab. Together with the earlier single-patient CLL report (Porter et al., NEJM 2011) and the first two children (Grupp et al., NEJM 2013), it established CAR-T as a realistic therapy and drove the pivotal ELIANA trial.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1056/NEJMoa1407222"},{"label":"First CLL patient report (Porter 2011)","url":"https://doi.org/10.1056/NEJMoa1103849"},{"label":"ClinicalTrials.gov NCT01626495","url":"https://clinicaltrials.gov/study/NCT01626495"}],"tags":[],"related":["paper-eliana-tisagenlecleucel-nejm-2018"],"cancers":["all-leukemia","cll"],"sections":[],"technologies":["car-t"],"targets":["cd19"],"drugs":["tisagenlecleucel"],"companies":["novartis"],"institutions":["penn-abramson"],"pathways":[],"terms":["crs","mrd-negative-cr"],"trials":[],"people":["carl-june","david-porter","bruce-levine"],"bottlenecks":["b-translational-valley","b-manufacturing-cell-therapy"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2014,"doi":"10.1056/NEJMoa1407222","authors":"Maude SL, Frey N, Shaw PA, et al.","paperType":"translational","findings":["30 patients (25 children, 5 adults) with relapsed/refractory ALL; 18 post-transplant, 3 blinatumomab-refractory.","Complete remission in 27 of 30 (90%); 22 of 27 MRD-negative by flow cytometry.","6-month event-free survival 67%; overall survival 78%; 19 patients in sustained remission at report.","CAR-T persistence and B-cell aplasia for up to 2 years in responders.","CRS in 100%, severe in 27%; reversed with tocilizumab; CD19-negative relapse identified as an escape mechanism."],"whatItMeans":"This paper is the proof-of-concept for a living drug: a single infusion of a patient's own engineered T cells could eradicate leukaemia that had survived chemotherapy, transplant and antibody therapy. It defined cytokine release syndrome and its antidote, tocilizumab, and revealed antigen-loss relapse. It led directly to the first approved gene-modified cell therapy three years later.","caveats":["Single-centre, uncontrolled series with short follow-up.","Selected patients able to wait for manufacturing and tolerate lymphodepletion.","Durability was uncertain; about a third relapsed within months, often with CD19-negative disease.","Toxicity management was still empirical."],"changedPractice":true,"participants":30},"route":"/key-papers/paper-maude-ctl019-all-nejm-2014/","neighbours":{"paper":[{"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","route":"/key-papers/paper-eliana-tisagenlecleucel-nejm-2018/"}],"cancer":[{"id":"all-leukemia","kind":"cancer","name":"Acute lymphoblastic leukaemia","route":"/cancers/all-leukemia/"},{"id":"cll","kind":"cancer","name":"Chronic lymphocytic leukaemia","route":"/cancers/cll/"}],"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":"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":"mrd-negative-cr","kind":"term","name":"MRD-negative complete remission","route":"/terms/mrd-negative-cr/"}],"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":"david-porter","kind":"person","name":"David L. Porter","route":"/people/david-porter/"},{"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-translational-valley","kind":"bottleneck","name":"The valley of death between lab and product","route":"/bottlenecks/b-translational-valley/"}],"journal":[{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}]}}