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

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

doi:10.1016/j.ymthe.2016.10.020

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

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

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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.

Original language	English
Pages (from-to)	285-295
Number of pages	11
Journal	Molecular Therapy
Volume	25
Issue number	1
DOIs	https://doi.org/10.1016/j.ymthe.2016.10.020
State	Published - Jan 4 2017

Keywords

CAR T
CD19
KTE-C19
diffuse large B cell lymphoma
refractory NHL

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10.1016/j.ymthe.2016.10.020

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Locke, F. L., Neelapu, S. S., Bartlett, N. L., Siddiqi, T., Chavez, J. C., Hosing, C. M., Ghobadi, A., Budde, L. E., Bot, A., Rossi, J. M., Jiang, Y., Xue, A. X., Elias, M., Aycock, J., Wiezorek, J., & Go, W. Y. (2017). Phase 1 Results of ZUMA-1: A Multicenter Study of KTE-C19 Anti-CD19 CAR T Cell Therapy in Refractory Aggressive Lymphoma. Molecular Therapy, 25(1), 285-295. https://doi.org/10.1016/j.ymthe.2016.10.020

@article{dda3c269c1284ff095e9837cc006f677,

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 × 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.",

keywords = "CAR T, CD19, KTE-C19, diffuse large B cell lymphoma, refractory NHL",

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

note = "Publisher Copyright: {\textcopyright} 2017 The Authors",

year = "2017",

month = jan,

day = "4",

doi = "10.1016/j.ymthe.2016.10.020",

language = "English",

volume = "25",

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journal = "Molecular Therapy",

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Locke, FL, Neelapu, SS, Bartlett, NL, Siddiqi, T, Chavez, JC, Hosing, CM, Ghobadi, A, Budde, LE, Bot, A, Rossi, JM, Jiang, Y, Xue, AX, Elias, M, Aycock, J, Wiezorek, J & Go, WY 2017, 'Phase 1 Results of ZUMA-1: A Multicenter Study of KTE-C19 Anti-CD19 CAR T Cell Therapy in Refractory Aggressive Lymphoma', Molecular Therapy, vol. 25, no. 1, pp. 285-295. https://doi.org/10.1016/j.ymthe.2016.10.020

TY - JOUR

T1 - Phase 1 Results of ZUMA-1

T2 - A Multicenter Study of KTE-C19 Anti-CD19 CAR T Cell Therapy in Refractory Aggressive Lymphoma

AU - Locke, Frederick L.

AU - Neelapu, Sattva S.

AU - Bartlett, Nancy L.

AU - Siddiqi, Tanya

AU - Chavez, Julio C.

AU - Hosing, Chitra M.

AU - Ghobadi, Armin

AU - Budde, Lihua E.

AU - Bot, Adrian

AU - Rossi, John M.

AU - Jiang, Yizhou

AU - Xue, Allen X.

AU - Elias, Meg

AU - Aycock, Jeff

AU - Wiezorek, Jeff

AU - Go, William Y.

PY - 2017/1/4

Y1 - 2017/1/4

N2 - 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.

AB - 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.

KW - CAR T

KW - CD19

KW - KTE-C19

KW - diffuse large B cell lymphoma

KW - refractory NHL

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U2 - 10.1016/j.ymthe.2016.10.020

DO - 10.1016/j.ymthe.2016.10.020

M3 - Article

C2 - 28129122

AN - SCOPUS:85016288763

SN - 1525-0016

VL - 25

SP - 285

EP - 295

JO - Molecular Therapy

JF - Molecular Therapy

IS - 1

ER -

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

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Keywords

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