Background:
Relapsed acute lymphoblastic leukemia (all) is difficult to treat despite the availability of aggressive therapies. chimeric antigen receptor-modified t cells targeting cd19 may overcome many limitations of conventional therapies and induce remission in patients with refractory disease.
Methods:
We infused autologous t cells transduced with a cd19-directed chimeric antigen receptor (ctl019) lentiviral vector in patients with relapsed or refractory all at doses of 0.76×10(6) to 20.6×10(6) ctl019 cells per kilogram of body weight. patients were monitored for a response, toxic effects, and the expansion and persistence of circulating ctl019 t cells.
Results:
A total of 30 children and adults received ctl019. complete remission was achieved in 27 patients (90%), including 2 patients with blinatumomab-refractory disease and 15 who had undergone stem-cell transplantation. ctl019 cells proliferated in vivo and were detectable in the blood, bone marrow, and cerebrospinal fluid of patients who had a response. sustained remission was achieved with a 6-month event-free survival rate of 67% (95% confidence interval [ci], 51 to 88) and an overall survival rate of 78% (95% ci, 65 to 95). at 6 months, the probability that a patient would have persistence of ctl019 was 68% (95% ci, 50 to 92) and the probability that a patient would have relapse-free b-cell aplasia was 73% (95% ci, 57 to 94). all the patients had the cytokine-release syndrome. severe cytokine-release syndrome, which developed in 27% of the patients, was associated with a higher disease burden before infusion and was effectively treated with the anti-interleukin-6 receptor antibody tocilizumab.
Conclusions:
Chimeric antigen receptor-modified t-cell therapy against cd19 was effective in treating relapsed and refractory all. ctl019 was associated with a high remission rate, even among patients for whom stem-cell transplantation had failed, and durable remissions up to 24 months were observed. (funded by novartis and others; cart19 clinicaltrials.gov numbers, nct01626495 and nct01029366.).