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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.
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, David L. Porter, Carl H. June, Tisagenlecleucel.
Shares Stephan A. Grupp, ELIANA: the global trial that made tisagenlecleucel the first approved CAR-T therapy for children and young adults with relapsed ALL, Tisagenlecleucel, Cytokine release syndrome (CRS).
Shares Stephan A. Grupp, Carl H. June, Tisagenlecleucel, Abramson Cancer Center, University of Pennsylvania.
Shares Tisagenlecleucel, Abramson Cancer Center, University of Pennsylvania, Cytokine release syndrome (CRS), Manufacturing cost and time for living and radioactive medicines.
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), Manufacturing cost and time for living and radioactive medicines, CD19.
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, CAR-T cell therapy.
Shares Tisagenlecleucel, Novartis, CAR-T cell therapy, Acute lymphoblastic leukaemia.
Shares Tisagenlecleucel, Cytokine release syndrome (CRS), Manufacturing cost and time for living and radioactive medicines, CD19.