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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.
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.
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.
The UCART19 report was the first clinical evidence that a universal, pre-manufactured CAR-T made from a donor can work, avoiding the weeks of autologous manufacturing and the problem of patients whose own T cells are too damaged. It set the template for later allogeneic programmes (including cemacabtagene autoleucel in the ALPHA studies) and for in vivo CAR generation. Short persistence and the need for deep lymphodepletion remain the central weaknesses.
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.
Shares Bruce L. Levine, ELIANA, Carl H. June, Tisagenlecleucel.
Shares Tisagenlecleucel, Abramson Cancer Center, University of Pennsylvania, ICANS (neurotoxicity), Cytokine release syndrome (CRS).
Shares Stephan A. Grupp, Carl H. June, Tisagenlecleucel, Abramson Cancer Center, University of Pennsylvania.
Shares Maude 2014: CD19 CAR-T cells produce complete remission in 27 of 30 children and adults with relapsed ALL, Tisagenlecleucel, Abramson Cancer Center, University of Pennsylvania, CD19.
Shares Tisagenlecleucel, ICANS (neurotoxicity), Cytokine release syndrome (CRS), Manufacturing cost and time for living and radioactive medicines.
Shares Tisagenlecleucel, ICANS (neurotoxicity), Cytokine release syndrome (CRS), Manufacturing cost and time for living and radioactive medicines.
Shares Obecabtagene autoleucel, Relapsed and refractory acute lymphoblastic leukaemia in children, CD19, CAR-T cell therapy.
Shares Tisagenlecleucel, ICANS (neurotoxicity), Cytokine release syndrome (CRS), Manufacturing cost and time for living and radioactive medicines.