Chimeric antigen receptor T cells for sustained remissions in leukemia.
Level 4 - case-series / case-control
Single-arm phase 1/2 interventional trial without a control group (case series)
PubMed 25317870 · doi:10.1056/NEJMoa1407222
What was done
Thirty children and adults with relapsed or refractory acute lymphoblastic leukemia received autologous T cells transduced with a CD19-directed chimeric antigen receptor lentiviral vector (CTL019) at doses of 0.76 x 10^6 to 20.6 x 10^6 cells per kilogram. Patients were monitored for clinical response, toxic effects, and in vivo expansion and persistence of CTL019 cells in blood, bone marrow, and cerebrospinal fluid.
What was found
Complete remission was achieved in 27 of 30 patients (90%), including 2 patients with blinatumomab-refractory disease and 15 who had previously undergone stem-cell transplantation. At 6 months, the event-free survival rate was 67% (95% CI, 51 to 88) and overall survival was 78% (95% CI, 65 to 95). The 6-month probability of CTL019 persistence was 68% (95% CI, 50 to 92) and relapse-free B-cell aplasia was 73% (95% CI, 57 to 94). Cytokine-release syndrome occurred in all 30 patients (100%), with severe cases in 27% responding to tocilizumab.
Why it matters
This study demonstrated that CD19-directed CAR T-cell therapy can achieve high complete remission rates in heavily pretreated and refractory acute lymphoblastic leukemia, including patients who relapsed after stem-cell transplantation.
Limits
The study was a small, single-arm trial with 30 participants and no comparator group. Cytokine-release syndrome was universal (100% of participants) with severe toxicity in over a quarter of patients, and follow-up was limited to a maximum of 24 months.
Cited by
- supports Following CAR-T cell therapy in 2012, pediatric leukemia patient Emily Whitehead remained cancer-free and matriculated as a pre-med student at the University of Pennsylvania.