[HTML][HTML] Long-term follow-up of CD19 CAR therapy in acute lymphoblastic leukemia

JH Park, I Rivière, M Gonen, X Wang… - … England Journal of …, 2018 - Mass Medical Soc
JH Park, I Rivière, M Gonen, X Wang, B Sénéchal, KJ Curran, C Sauter, Y Wang…
New England Journal of Medicine, 2018Mass Medical Soc
Background CD19-specific chimeric antigen receptor (CAR) T cells induce high rates of
initial response among patients with relapsed B-cell acute lymphoblastic leukemia (ALL)
and long-term remissions in a subgroup of patients. Methods We conducted a phase 1 trial
involving adults with relapsed B-cell ALL who received an infusion of autologous T cells
expressing the 19-28z CAR at the Memorial Sloan Kettering Cancer Center (MSKCC).
Safety and long-term outcomes were assessed, as were their associations with …
Background
CD19-specific chimeric antigen receptor (CAR) T cells induce high rates of initial response among patients with relapsed B-cell acute lymphoblastic leukemia (ALL) and long-term remissions in a subgroup of patients.
Methods
We conducted a phase 1 trial involving adults with relapsed B-cell ALL who received an infusion of autologous T cells expressing the 19-28z CAR at the Memorial Sloan Kettering Cancer Center (MSKCC). Safety and long-term outcomes were assessed, as were their associations with demographic, clinical, and disease characteristics.
Results
A total of 53 adults received 19-28z CAR T cells that were manufactured at MSKCC. After infusion, severe cytokine release syndrome occurred in 14 of 53 patients (26%; 95% confidence interval [CI], 15 to 40); 1 patient died. Complete remission was observed in 83% of the patients. At a median follow-up of 29 months (range, 1 to 65), the median event-free survival was 6.1 months (95% CI, 5.0 to 11.5), and the median overall survival was 12.9 months (95% CI, 8.7 to 23.4). Patients with a low disease burden (<5% bone marrow blasts) before treatment had markedly enhanced remission duration and survival, with a median event-free survival of 10.6 months (95% CI, 5.9 to not reached) and a median overall survival of 20.1 months (95% CI, 8.7 to not reached). Patients with a higher burden of disease (≥5% bone marrow blasts or extramedullary disease) had a greater incidence of the cytokine release syndrome and neurotoxic events and shorter long-term survival than did patients with a low disease burden.
Conclusions
In the entire cohort, the median overall survival was 12.9 months. Among patients with a low disease burden, the median overall survival was 20.1 months and was accompanied by a markedly lower incidence of the cytokine release syndrome and neurotoxic events after 19-28z CAR T-cell infusion than was observed among patients with a higher disease burden. (Funded by the Commonwealth Foundation for Cancer Research and others; ClinicalTrials.gov number, NCT01044069.)
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