Maude 2014: CD19 CAR-T cells produce complete remission in 27 of 30 children and adults with relapsed ALL
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.
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.
- 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.
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.
- 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.
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not linked directly; found by shared links- PersonEmily Whitehead
Shares Bruce L. Levine, David L. Porter, Carl H. June, Tisagenlecleucel.
- TrialELIANA
Shares Tisagenlecleucel, ELIANA: the global trial that made tisagenlecleucel the first approved CAR-T therapy for children and young adults with relapsed ALL, Cytokine release syndrome (CRS), CD19.
- InstitutionChildren's Hospital of Philadelphia
Shares Carl H. June, Tisagenlecleucel, Abramson Cancer Center, University of Pennsylvania, Novartis.
- Key paperJULIET: tisagenlecleucel for adults with relapsed or refractory diffuse large B-cell lymphoma
Shares Tisagenlecleucel, Abramson Cancer Center, University of Pennsylvania, Novartis, Cytokine release syndrome (CRS).
- Key paperUCART19: the first gene-edited, donor-derived CAR-T cells in children and adults with relapsed B-cell ALL
Shares ELIANA: the global trial that made tisagenlecleucel the first approved CAR-T therapy for children and young adults with relapsed ALL, Cytokine release syndrome (CRS), CD19, Manufacturing cost and time for living and radioactive medicines.
- ProductObecabtagene autoleucel
Shares ELIANA: the global trial that made tisagenlecleucel the first approved CAR-T therapy for children and young adults with relapsed ALL, Cytokine release syndrome (CRS), CD19, Acute lymphoblastic leukaemia.
- ProductBrexucabtagene autoleucel
Shares Cytokine release syndrome (CRS), CD19, Acute lymphoblastic leukaemia, CAR-T cell therapy.
- IdeaTwo-day CAR-T manufacture paired with rapid release tests that regulators accept
Shares Novartis, Manufacturing cost and time for living and radioactive medicines, CAR-T cell therapy.