Phase 1 Results of ZUMA-1: A Multicenter Study of KTE-C19 Anti-CD19 CAR T Cell Therapy in Refractory Aggressive Lymphoma.
Mol Ther
; 25(1): 285-295, 2017 Jan 04.
Article
en En
| MEDLINE
| ID: mdl-28129122
ABSTRACT
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Linfoma no Hodgkin
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Proteínas Recombinantes de Fusión
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Linfocitos T
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Complejo Receptor-CD3 del Antígeno de Linfocito T
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Antígenos CD28
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Antígenos CD19
Tipo de estudio:
Clinical_trials
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Diagnostic_studies
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Observational_studies
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Prognostic_studies
/
Risk_factors_studies
Límite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Mol Ther
Asunto de la revista:
BIOLOGIA MOLECULAR
/
TERAPEUTICA
Año:
2017
Tipo del documento:
Article