[HTML][HTML] Chimeric antigen receptor T cells for sustained remissions in leukemia

SL Maude, N Frey, PA Shaw, R Aplenc… - … England Journal of …, 2014 - Mass Medical Soc
SL Maude, N Frey, PA Shaw, R Aplenc, DM Barrett, NJ Bunin, A Chew, VE Gonzalez…
New England Journal of Medicine, 2014Mass Medical Soc
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× 106 to 20.6× 106 CTL019 cells per kilogram of body …
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 0.76×106 to 20.6×106 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.)
The New England Journal Of Medicine