Chimeric antigen receptor T cells persist and induce sustained remissions in relapsed refractory chronic lymphocytic leukemia

DL Porter, WT Hwang, NV Frey, SF Lacey… - Science translational …, 2015 - science.org
DL Porter, WT Hwang, NV Frey, SF Lacey, PA Shaw, AW Loren, A Bagg, KT Marcucci…
Science translational medicine, 2015science.org
Patients with multiply relapsed or refractory chronic lymphocytic leukemia (CLL) have a poor
prognosis. Chimeric antigen receptor (CAR)–modified T cells targeting CD19 have the
potential to improve on the low complete response rates with conventional therapies by
inducing sustained remissions in patients with refractory B cell malignancies. We previously
reported preliminary results on three patients with refractory CLL. We report the mature
results from our initial trial using CAR-modified T cells to treat 14 patients with relapsed and …
Patients with multiply relapsed or refractory chronic lymphocytic leukemia (CLL) have a poor prognosis. Chimeric antigen receptor (CAR)–modified T cells targeting CD19 have the potential to improve on the low complete response rates with conventional therapies by inducing sustained remissions in patients with refractory B cell malignancies. We previously reported preliminary results on three patients with refractory CLL. We report the mature results from our initial trial using CAR-modified T cells to treat 14 patients with relapsed and refractory CLL. Autologous T cells transduced with a CD19-directed CAR (CTL019) lentiviral vector were infused into patients with relapsed/refractory CLL at doses of 0.14 × 108 to 11 × 108 CTL019 cells (median, 1.6 × 108 cells). Patients were monitored for toxicity, response, expansion, and persistence of circulating CTL019 T cells. The overall response rate in these heavily pretreated CLL patients was 8 of 14 (57%), with 4 complete remissions (CR) and 4 partial remissions (PR). The in vivo expansion of the CAR T cells correlated with clinical responses, and the CAR T cells persisted and remained functional beyond 4 years in the first two patients achieving CR. No patient in CR has relapsed. All responding patients developed B cell aplasia and experienced cytokine release syndrome, coincident with T cell proliferation. Minimal residual disease was not detectable in patients who achieved CR, suggesting that disease eradication may be possible in some patients with advanced CLL.
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