CD22-directed CAR T-cell therapy induces complete remissions in CD19-directed CAR-refractory large B-cell lymphoma

被引：68

作者：

Baird, John H. ^{[1
,2
]}

Frank, Matthew J. ^{[1
,2
]}

Craig, Juliana ^{[1
,2
]}

Patel, Shabnum ^{[2
]}

Spiegel, Jay Y. ^{[1
,2
]}

Sahaf, Bita ^{[2
]}

Oak, Jean S. ^{[3
]}

Younes, Sheren F. ^{[3
]}

Ozawa, Michael G. ^{[3
]}

Yang, Eric ^{[3
]}

Natkunam, Yasodha ^{[3
]}

Tamaresis, John ^{[4
]}

Ehlinger, Zachary ^{[2
]}

Reynolds, Warren D. ^{[2
]}

Arai, Sally ^{[1
]}

Johnston, Laura ^{[1
]}

Lowsky, Robert ^{[1
]}

Meyer, Everett ^{[1
,2
]}

Negrin, Robert S. ^{[1
]}

Rezvani, Andrew R. ^{[1
]}

Shiraz, Parveen ^{[1
,2
]}

Sidana, Surbhi ^{[1
,2
]}

Weng, Wen-Kai ^{[1
]}

Davis, Kara L. ^{[5
]}

Ramakrishna, Sneha ^{[5
]}

Schultz, Liora ^{[5
]}

Mullins, Chelsea ^{[6
]}

Jacob, Allison ^{[6
]}

Kirsch, Ilan ^{[6
]}

Feldman, Steven A. ^{[2
]}

Mackall, Crystal L. ^{[1
,2
,5
]}

Miklos, David B. ^{[1
,2
]}

Muffly, Lori ^{[1
,2
]}

机构：

[1] Stanford Univ, Sch Med, Dept Med, Div Blood & Marrow Transplantat, Stanford, CA 94305 USA

[2] Stanford Univ, Ctr Canc Cell Therapy, Stanford Canc Inst, Stanford, CA 94305 USA

[3] Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA

[4] Stanford Univ, Sch Med, Dept Biomed Data Sci, Stanford, CA 94305 USA

[5] Stanford Univ, Sch Med, Dept Pediat, Div Hematol Oncol, Stanford, CA 94305 USA

[6] Adapt Biotechnol, Seattle, WA USA

来源：

BLOOD | 2021年 / 137卷 / 17期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1182/blood.2020009432

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

The prognosis of patients with large B-cell lymphoma (LBCL) that progresses after treatment with chimeric antigen receptor (CAR) T-cell therapy targeting CD19 (CAR19) is poor. We report on the first 3 consecutive patients with autologous CAR19-refractory LBCL who were treated with a single infusion of autologous 1 x 10(6) CAR(+) T cells per kilogram targeting CD22 (CAR22) as part of a phase 1 dose-escalation study. CAR22 therapy was relatively well tolerated, without any observed nonhematologic adverse events higher than grade 2. After infusion, all 3 patients achieved complete remission, with all responses continuing at the time of last follow-up (mean, 7.8 months; range, 6-9.3). Circulating CAR22 cells demonstrated robust expansion (peak range, 85.4-350 cells per microliter), and persisted beyond 3 months in all patients with continued radiographic responses and corresponding decreases in circulating tumor DNA beyond 6 months after infusion. Further accrual at a higher dose level in this phase 1 dose-escalation study is ongoing and will explore the role of this therapy in patients in whom prior CAR T-cell therapies have failed.

引用

页码：2321 / 2325

页数：5

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