{"entity":{"id":"tisagenlecleucel","kind":"drug","name":"Tisagenlecleucel","aka":[],"tldr":"Tisagenlecleucel was the first CAR-T therapy ever approved (2017), for children and young adults whose leukaemia had come back after everything else.","summary":"ELIANA (n=75 infused, age ≤25): ORR 81% within 3 months, 12-month OS 76%, 5-year EFS ~44% in responders without further therapy (2023 update). Approved 30 August 2017 for relapsed/refractory B-ALL up to age 25; later for DLBCL and follicular lymphoma. 4-1BB costimulation gives long persistence; CD19-negative relapse is the main failure mode. Emily Whitehead, treated in 2012, remains in remission.","status":"approved","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Tisagenlecleucel","links":[{"label":"FDA label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Tisagenlecleucel"}],"tags":[],"related":[],"cancers":["all-leukemia","all-paediatric-relapsed","dlbcl"],"sections":[],"technologies":["car-t"],"targets":["cd19"],"drugs":[],"companies":["novartis"],"institutions":[],"pathways":[],"terms":["crs","icans"],"trials":["eliana","nct04094311","nct05888493","nct03876769"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Kymriah","code":"CTL019","modality":"CAR-T (CD19)","mechanism":"Autologous T cells transduced with a lentiviral CD19 scFv-4-1BB-CD3ζ CAR; expand in vivo and kill CD19+ blasts.","approvals":[{"region":"US","year":2017,"indication":"Relapsed/refractory B-ALL, patients up to 25 years"},{"region":"US","year":2018,"indication":"Relapsed/refractory DLBCL"},{"region":"US","year":2022,"indication":"Relapsed/refractory follicular lymphoma"}],"mechanismSteps":["Leukapheresis collects the patient's T cells","Lentivirus inserts the CD19 CAR gene; cells expand for ~3 weeks","Lymphodepleting fludarabine/cyclophosphamide makes room","Infused CAR-T cells find CD19 on blasts and kill them, expanding a thousand-fold (CRS risk)","Persisting CAR-T cells cause B-cell aplasia, a marker of ongoing activity"],"dosing":{"route":"Single IV infusion","schedule":"0.2-5.0 × 10^6 CAR+ cells/kg (≤50 kg) or 0.1-2.5 × 10^8 (>50 kg) after lymphodepletion","monitoring":"CRS and ICANS (boxed warning; tocilizumab on site), prolonged cytopenias, hypogammaglobulinaemia, secondary T-cell malignancy (class warning 2024)","source":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=Kymriah"},"toxicity":[{"event":"Cytokine release syndrome","anyGradePct":77,"grade3PlusPct":46,"source":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=Kymriah","note":"ELIANA, Penn grading"},{"event":"Neurotoxicity (ICANS)","anyGradePct":40,"grade3PlusPct":13},{"event":"Prolonged cytopenias","grade3PlusPct":32},{"event":"B-cell aplasia / hypogammaglobulinaemia","note":"Expected; IVIG replacement"}],"access":[],"regulatoryEvents":[{"date":"2017-08-30","type":"approval","region":"US","note":"First CAR-T approval in history"},{"date":"2022-05-27","type":"accelerated-approval","region":"US","note":"Accelerated approval on a surrogate endpoint; the confirmatory requirement was still open 4.3 years later, when the FDA's table was read.","indication":"Treatment of adult patients with relapsed or refractory (r/r) follicular lymphoma (FL) after two or more lines of systemic therapy"},{"date":"2024-04-18","type":"label-change","region":"US","note":"Class boxed warning for T-cell malignancies"},{"date":"2025-06-27","type":"label-change","region":"US","note":"REMS requirements removed for approved CAR-T products"}]},"route":"/drugs/tisagenlecleucel/","neighbours":{"cancer":[{"id":"all-leukemia","kind":"cancer","name":"Acute lymphoblastic leukaemia","route":"/cancers/all-leukemia/"},{"id":"childhood-cancers","kind":"cancer","name":"Childhood cancers (all types)","route":"/cancers/childhood-cancers/"},{"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/"},{"id":"all-paediatric-high-risk","kind":"cancer","name":"High-risk acute lymphoblastic leukaemia in children (high-risk B-ALL and T-ALL)","route":"/cancers/all-paediatric-high-risk/"},{"id":"all-infant","kind":"cancer","name":"Infant acute lymphoblastic leukaemia (KMT2A-rearranged, under one year)","route":"/cancers/all-infant/"},{"id":"leukaemia","kind":"cancer","name":"Leukaemia (all types)","route":"/cancers/leukaemia/"},{"id":"all-ph-like","kind":"cancer","name":"Philadelphia chromosome-like acute lymphoblastic leukaemia (Ph-like or BCR::ABL1-like ALL)","route":"/cancers/all-ph-like/"},{"id":"all-paediatric-ph-positive","kind":"cancer","name":"Philadelphia chromosome-positive acute lymphoblastic leukaemia in children (Ph-positive ALL)","route":"/cancers/all-paediatric-ph-positive/"},{"id":"all-paediatric-relapsed","kind":"cancer","name":"Relapsed and refractory acute lymphoblastic leukaemia in children","route":"/cancers/all-paediatric-relapsed/"},{"id":"all-paediatric-standard-risk","kind":"cancer","name":"Standard-risk B-cell acute lymphoblastic leukaemia in children","route":"/cancers/all-paediatric-standard-risk/"}],"technology":[{"id":"car-t-manufacturing-process","kind":"technology","name":"Autologous CAR-T manufacturing, batch by batch","route":"/technologies/car-t-manufacturing-process/"},{"id":"car-t","kind":"technology","name":"CAR-T cell therapy","route":"/technologies/car-t/"}],"target":[{"id":"cd19","kind":"target","name":"CD19","route":"/targets/cd19/"}],"company":[{"id":"novartis","kind":"company","name":"Novartis","route":"/companies/novartis/"}],"term":[{"id":"crs","kind":"term","name":"Cytokine release syndrome (CRS)","route":"/terms/crs/"},{"id":"lymphoma-tx-crs-icans","kind":"term","name":"Cytokine release syndrome and ICANS: grading and management","route":"/terms/lymphoma-tx-crs-icans/"},{"id":"icans","kind":"term","name":"ICANS (neurotoxicity)","route":"/terms/icans/"},{"id":"lymphoma-tx-immunoglobulin-replacement","kind":"term","name":"Immunoglobulin replacement after CAR-T, bispecifics and long anti-CD20 treatment","route":"/terms/lymphoma-tx-immunoglobulin-replacement/"},{"id":"lymphoma-tx-failed-and-negative","kind":"term","name":"Lymphoma treatments that did not work: the negative trials worth knowing","route":"/terms/lymphoma-tx-failed-and-negative/"},{"id":"lymphoma-tx-pod24","kind":"term","name":"POD24: progression of follicular lymphoma within two years, and why it changes the plan","route":"/terms/lymphoma-tx-pod24/"},{"id":"lymphoma-tx-car-t-pathway","kind":"term","name":"The CAR-T pathway in lymphoma: referral, apheresis, bridging and the waiting","route":"/terms/lymphoma-tx-car-t-pathway/"},{"id":"lymphoma-tx-uk-access","kind":"term","name":"What the NHS in England funds for lymphoma, appraisal by appraisal","route":"/terms/lymphoma-tx-uk-access/"}],"trial":[{"id":"nct05888493","kind":"trial","name":"A Phase III Trial Comparing Tisagenlecleucel to Standard of Care (SoC) in Adult Participants With r/r Follicular Lymphoma","route":"/trials/nct05888493/"},{"id":"elara","kind":"trial","name":"ELARA","route":"/trials/elara/"},{"id":"eliana","kind":"trial","name":"ELIANA","route":"/trials/eliana/"},{"id":"juliet","kind":"trial","name":"JULIET","route":"/trials/juliet/"},{"id":"nct03876769","kind":"trial","name":"Study of Efficacy and Safety of Tisagenlecleucel in HR B-ALL EOC MRD Positive Patients","route":"/trials/nct03876769/"},{"id":"nct04094311","kind":"trial","name":"Study of Out of Specification for Tisagenlecleucel","route":"/trials/nct04094311/"}],"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/"},{"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-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-belinda-tisagenlecleucel-second-line-nejm-2022","kind":"paper","name":"Second-line tisagenlecleucel or standard care in aggressive B-cell lymphoma","route":"/key-papers/paper-belinda-tisagenlecleucel-second-line-nejm-2022/"},{"id":"paper-elara-tisagenlecleucel-follicular-nat-med-2022","kind":"paper","name":"Tisagenlecleucel in adult relapsed or refractory follicular lymphoma: the phase 2 ELARA trial","route":"/key-papers/paper-elara-tisagenlecleucel-follicular-nat-med-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/"},{"id":"paediatric-oncology-roadmap","kind":"roadmap","name":"Paediatric oncology roadmap: cooperative-group cures → engineered immunity → drugs developed for children first","route":"/roadmaps/paediatric-oncology-roadmap/"}],"idea":[{"id":"lymphoma-ev-manufacturing-time-as-a-trial-endpoint","kind":"idea","name":"Report the time from apheresis to infusion as a trial endpoint, not a logistics footnote","route":"/ideas/lymphoma-ev-manufacturing-time-as-a-trial-endpoint/"}],"person":[{"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":"emily-whitehead","kind":"person","name":"Emily Whitehead","route":"/people/emily-whitehead/"},{"id":"sherry-lansing","kind":"person","name":"Sherry Lansing","route":"/people/sherry-lansing/"}],"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-drug-pricing","kind":"bottleneck","name":"Prices and value","route":"/bottlenecks/b-drug-pricing/"}],"institution":[{"id":"chop","kind":"institution","name":"Children's Hospital of Philadelphia","route":"/institutions/chop/"}],"drug":[{"id":"talicabtagene-autoleucel","kind":"drug","name":"Talicabtagene autoleucel","route":"/drugs/talicabtagene-autoleucel/"},{"id":"tocilizumab","kind":"drug","name":"Tocilizumab","route":"/drugs/tocilizumab/"},{"id":"varnimcabtagene-autoleucel","kind":"drug","name":"Varnimcabtagene autoleucel","route":"/drugs/varnimcabtagene-autoleucel/"}],"biomarker":[{"id":"cd19-expression","kind":"biomarker","name":"CD19 expression (CD19-positive)","route":"/biomarkers/cd19-expression/"}]}}