Phase 1 Results of ZUMA-1: A Multicenter Study of KTE-C19 Anti-CD19 CAR T Cell Therapy in Refractory Aggressive Lymphoma
By F. Locke, S. Neelapu, N. Bartlett, T. Siddiqi, J. Chavez, C. Hosing, A. Ghobadi, L. Budde, A. Bot, J. Rossi and 6 more. Molecular Therapy, 2017
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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.
Subfields: Biomedical Engineering, Electrical and Electronic Engineering, Oncology
View Paper: https://www.semanticscholar.org/paper/f01415ec4cf6a3ddaffe4d4e07fabeda3595e84f
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Citations in the corpus
- Recent advances in CAR T-cell toxicity: Mechanisms, manifestations and management (2018, background): “Patients may develop dyspnea and hypoxia due to pulmonary edema in the setting of a capillary leak syndrome caused by circulating cytokines [7,8,11,21,22].”
- Cytokine release syndrome (2018, background): “Interestingly, in some studies even glucocorticoids did not seem to impact response rates [39, 78, 80].”
- Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma (2017, unknown): “Relapse after autologous stem-cell transplantation 16 (21) 5 (21) 21 (21)”