Journal Article

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

Siddiqi, Tanya, Go, William Y., Jiang, Yizhou, Ghobadi, Armin, Locke, Frederick L., Aycock, Jeff, Bot, Adrian, Hosing, Chitra M., Wiezorek, Jeff, Chavez, Julio C., Xue, Allen X., Neelapu, Sattva S., Rossi, John M., Elias, Meg, Bartlett, Nancy L., Budde, Lihua E.

2017

Overview

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. In a multicenter phase 1 study, Locke, Neelapu, et al. report tolerability and safety of KTE-C19, a CD19 chimeric antigen receptor technology, in patients with chemorefractory DLBCL. More importantly, KTE-C19 could provide durable clinical benefit in this difficult-to-treat patient population, demonstrating broad clinical applicability of KTE-C19.

• Publisher: Elsevier Inc,Elsevier Limited,American Society of Gene & Cell Therapy
• Subject: Adult / Aged / Antigens, CD19 - immunology / Antineoplastic Combined Chemotherapy Protocols - therapeutic use / B-cell lymphoma / Biomarkers / CAR T / Cardiac arrhythmia / CD19 / CD19 antigen / CD28 antigen / CD28 Antigens - genetics / CD28 Antigens - metabolism / Chemotherapy / Chimeric antigen receptors / Combined Modality Therapy / Cyclophosphamide / Cytokines / Delirium / diffuse large B cell lymphoma / Disease Progression / Drug Resistance, Neoplasm / Female / Fludarabine / Follow-Up Studies / Humans / Hypoxia / Immunophenotyping / Immunotherapy, Adoptive - adverse effects / Immunotherapy, Adoptive - methods / Kidneys / KTE-C19 / Lymphocytes / Lymphocytes B / Lymphocytes T / Lymphoma / Lymphoma, Large B-Cell, Diffuse - diagnosis / Lymphoma, Large B-Cell, Diffuse - immunology / Lymphoma, Large B-Cell, Diffuse - therapy / Lymphoma, Non-Hodgkin - diagnosis / Lymphoma, Non-Hodgkin - immunology / Lymphoma, Non-Hodgkin - therapy / Male / Metabolism / Middle Aged / Neoplasm Staging / Neurotoxicity / Neutropenia / Original / Patients / Receptor-CD3 Complex, Antigen, T-Cell - genetics / Receptor-CD3 Complex, Antigen, T-Cell - metabolism / Recombinant Fusion Proteins / refractory NHL / Sepsis / T-Lymphocytes - immunology / T-Lymphocytes - metabolism / Treatment Outcome