[HTML][HTML] Phase 1 results of ZUMA-1: a multicenter study of KTE-C19 anti-CD19 CAR T cell therapy in refractory aggressive lymphoma
FL Locke, SS Neelapu, NL Bartlett, T Siddiqi… - Molecular Therapy, 2017 - cell.com
FL Locke, SS Neelapu, NL Bartlett, T Siddiqi, JC Chavez, CM Hosing, A Ghobadi, LE Budde…
Molecular Therapy, 2017•cell.comOutcomes for patients with refractory diffuse large B cell lymphoma (DLBCL) are poor. In the
multicenter ZUMA-1 phase 1 study, we evaluated KTE-C19, an autologous CD3ζ/CD28-
based chimeric antigen receptor (CAR) T cell therapy, in patients with refractory DLBCL.
Patients received low-dose conditioning chemotherapy with concurrent cyclophosphamide
(500 mg/m 2) and fludarabine (30 mg/m 2) for 3 days followed by KTE-C19 at a target dose
of 2× 10 6 CAR T cells/kg. The incidence of dose-limiting toxicity (DLT) was the primary …
multicenter ZUMA-1 phase 1 study, we evaluated KTE-C19, an autologous CD3ζ/CD28-
based chimeric antigen receptor (CAR) T cell therapy, in patients with refractory DLBCL.
Patients received low-dose conditioning chemotherapy with concurrent cyclophosphamide
(500 mg/m 2) and fludarabine (30 mg/m 2) for 3 days followed by KTE-C19 at a target dose
of 2× 10 6 CAR T cells/kg. The incidence of dose-limiting toxicity (DLT) was the primary …
Outcomes for patients with refractory diffuse large B cell lymphoma (DLBCL) are poor. In the multicenter ZUMA-1 phase 1 study, we evaluated KTE-C19, an autologous CD3ζ/CD28-based chimeric antigen receptor (CAR) T cell therapy, in patients with refractory DLBCL. Patients received low-dose conditioning chemotherapy with concurrent cyclophosphamide (500 mg/m2) and fludarabine (30 mg/m2) for 3 days followed by KTE-C19 at a target dose of 2 × 106 CAR T cells/kg. The incidence of dose-limiting toxicity (DLT) was the primary endpoint. Seven patients were treated with KTE-C19 and one patient experienced a DLT of grade 4 cytokine release syndrome (CRS) and neurotoxicity. Grade ≥3 CRS and neurotoxicity were observed in 14% (n = 1/7) and 57% (n = 4/7) of patients, respectively. All other KTE-C19-related grade ≥3 events resolved within 1 month. The overall response rate was 71% (n = 5/7) and complete response (CR) rate was 57% (n = 4/7). Three patients have ongoing CR (all at 12+ months). CAR T cells demonstrated peak expansion within 2 weeks and continued to be detectable at 12+ months in patients with ongoing CR. This regimen of KTE-C19 was safe for further study in phase 2 and induced durable remissions in patients with refractory DLBCL.
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