title: 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 × 106CAR 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.affiliation: Department of Blood and Marrow Transplantation, Moffitt Cancer Center, Tampa, FL 33612, USA. Electronic address: frederick.locke@moffitt.org.
authors.forename: Frederick L
authors.initials: FL
authors.lastname: Locke
authors.affiliation: Division of Cancer Medicine, Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Sattva S
authors.initials: SS
authors.lastname: Neelapu
authors.affiliation: Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Bartlett
authors.affiliation: Department of Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA 91010, USA.
authors.forename: Tanya
authors.initials: T
authors.lastname: Siddiqi
authors.affiliation: Department of Malignant Hematology, Moffitt Cancer Center, Tampa, FL 33612, USA.
authors.forename: Julio C
authors.initials: JC
authors.lastname: Chavez
authors.affiliation: Division of Cancer Medicine, Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Chitra M
authors.initials: CM
authors.lastname: Hosing
authors.affiliation: Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Armin
authors.initials: A
authors.lastname: Ghobadi
authors.affiliation: Department of Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA 91010, USA.
authors.forename: Lihua E
authors.initials: LE
authors.lastname: Budde
authors.affiliation: Kite Pharma, Santa Monica, CA 90404, USA.
authors.forename: Adrian
authors.initials: A
authors.lastname: Bot
authors.affiliation: Kite Pharma, Santa Monica, CA 90404, USA.
authors.forename: John M
authors.initials: JM
authors.lastname: Rossi
authors.affiliation: Kite Pharma, Santa Monica, CA 90404, USA.
authors.forename: Yizhou
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Kite Pharma, Santa Monica, CA 90404, USA.
authors.forename: Allen X
authors.initials: AX
authors.lastname: Xue
authors.affiliation: Kite Pharma, Santa Monica, CA 90404, USA.
authors.forename: Meg
authors.initials: M
authors.lastname: Elias
authors.affiliation: Kite Pharma, Santa Monica, CA 90404, USA.
authors.forename: Jeff
authors.initials: J
authors.lastname: Aycock
authors.affiliation: Kite Pharma, Santa Monica, CA 90404, USA.
authors.forename: Jeff
authors.initials: J
authors.lastname: Wiezorek
authors.affiliation: Kite Pharma, Santa Monica, CA 90404, USA.
authors.forename: William Y
authors.initials: WY
authors.lastname: Go
mesh_terms: D000328:Adult; D000368:Aged; D018941:Antigens, CD19 / Q000276:immunology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D015415:Biomarkers; D018106:CD28 Antigens / Q000235:genetics / Q000378:metabolism*; D003131:Combined Modality Therapy; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016130:Immunophenotyping; D016219:Immunotherapy, Adoptive / Q000009:adverse effects / Q000379:methods; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis / Q000276:immunology / Q000628:therapy; D008228:Lymphoma, Non-Hodgkin / Q000175:diagnosis / Q000276:immunology* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D018941:Antigens, CD19; D015415:Biomarkers; D018106:CD28 Antigens; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D011993:Recombinant Fusion Proteins
keywords: CAR T; CD19; KTE-C19; diffuse large B cell lymphoma; refractory NHL