Phase 1 Results of ZUMA-1: A Multicenter Study of KTE-C19 Anti-CD19 CAR T Cell Therapy in Refractory Aggressive Lymphoma.

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.

• Authors: Frederick L Locke, Sattva S Neelapu, Nancy L Bartlett, Tanya Siddiqi, Julio C Chavez, Chitra M Hosing, Armin Ghobadi, Lihua E Budde, Adrian Bot, John M Rossi, Yizhou Jiang, Allen X Xue, Meg Elias, Jeff Aycock, Jeff Wiezorek, William Y Go
• Journal: Molecular therapy : the journal of the American Society of Gene Therapy (Mol Ther) Vol. 25 Issue 1 Pg. 285-295 (Jan 04 2017) ISSN: 1525-0024 [Electronic] United States
• PMID: 28129122 (Publication Type: Clinical Trial, Phase I, Journal Article, Multicenter Study)
• Copyright: Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antigens, CD19
• Biomarkers
• CD28 Antigens
• Receptor-CD3 Complex, Antigen, T-Cell
• Recombinant Fusion Proteins

Topics

• Adult
• Aged
• Antigens, CD19 (immunology)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Biomarkers
• CD28 Antigens (genetics, metabolism)
• Combined Modality Therapy
• Disease Progression
• Drug Resistance, Neoplasm
• Female
• Follow-Up Studies
• Humans
• Immunophenotyping
• Immunotherapy, Adoptive (adverse effects, methods)
• Lymphoma, Large B-Cell, Diffuse (diagnosis, immunology, therapy)
• Lymphoma, Non-Hodgkin (diagnosis, immunology, therapy)
• Male
• Middle Aged
• Neoplasm Staging
• Receptor-CD3 Complex, Antigen, T-Cell (genetics, metabolism)
• Recombinant Fusion Proteins
• T-Lymphocytes (immunology, metabolism)
• Treatment Outcome