Lymphoma Remissions Caused by Anti-CD19 Chimeric Antigen Receptor T Cells Are Associated With High Serum Interleukin-15 Levels

被引：451

作者：

Kochenderfer, James N. ^{[1
]}

Somerville, Robert P. T. ^{[1
]}

Lu, Tangying ^{[1
]}

Shi, Victoria ^{[1
]}

Bot, Adrian ^{[2
]}

Rossi, John ^{[2
]}

Xue, Allen ^{[2
]}

Goff, Stephanie L. ^{[1
]}

Yang, James C. ^{[1
]}

Sherry, Richard M. ^{[1
]}

Klebanoff, Christopher A. ^{[1
]}

Kammula, Udai S. ^{[1
]}

Sherman, Marika ^{[2
]}

Perez, Arianne ^{[2
]}

Yuan, Constance M. ^{[1
]}

Feldman, Tatyana ^{[3
]}

Friedberg, Jonathan W. ^{[4
]}

Roschewski, Mark J. ^{[1
]}

Feldman, Steven A. ^{[1
]}

McIntyre, Lori ^{[1
]}

Toomey, Mary Ann ^{[1
]}

Rosenberg, Steven A. ^{[1
]}

机构：

[1] NCI, NIH, Bethesda, MD 20892 USA

[2] Kite Pharma, Santa Monica, CA USA

[3] Hackensack Univ, John Theurer Canc Ctr, Med Ctr, Hackensack, NJ USA

[4] Univ Rochester, Sch Med, Rochester, NY USA

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2017年 / 35卷 / 16期

基金：

美国国家卫生研究院;

关键词：

B-CELL; ADOPTIVE IMMUNOTHERAPY; TRANSPLANTATION; THERAPY; CANCER; CD19; MALIGNANCIES; LYMPHOCYTES; EXPANSION; LEUKEMIA;

D O I：

10.1200/JCO.2016.71.3024

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

PurposeT cells genetically modified to express chimeric antigen receptors (CARs) targeting CD19 (CAR-19) have potent activity against acute lymphoblastic leukemia, but fewer results supporting treatment of lymphoma with CAR-19 T cells have been published. Patients with lymphoma that is chemotherapy refractory or relapsed after autologous stem-cell transplantation have a grim prognosis, and new treatments for these patients are clearly needed. Chemotherapy administered before adoptive T-cell transfer has been shown to enhance the antimalignancy activity of adoptively transferred T cells.Patients and MethodsWe treated 22 patients with advanced-stage lymphoma in a clinical trial of CAR-19 T cells preceded by low-dose chemotherapy. Nineteen patients had diffuse large B-cell lymphoma, two patients had follicular lymphoma, and one patient had mantle cell lymphoma. Patients received a single dose of CAR-19 T cells 2 days after a low-dose chemotherapy conditioning regimen of cyclophosphamide plus fludarabine.ResultsThe overall remission rate was 73% with 55% complete remissions and 18% partial remissions. Eleven of 12 complete remissions are ongoing. Fifty-five percent of patients had grade 3 or 4 neurologic toxicities that completely resolved. The low-dose chemotherapy conditioning regimen depleted blood lymphocytes and increased serum interleukin-15 (IL-15). Patients who achieved a remission had a median peak blood CAR(+) cell level of 98/L and those who did not achieve a remission had a median peak blood CAR(+) cell level of 15/L (P = .027). High serum IL-15 levels were associated with high peak blood CAR(+) cell levels (P = .001) and remissions of lymphoma (P < .001).ConclusionCAR-19 T cells preceded by low-dose chemotherapy induced remission of advanced-stage lymphoma, and high serum IL-15 levels were associated with the effectiveness of this treatment regimen. CAR-19 T cells will likely become an important treatment for patients with relapsed lymphoma.

引用

页码：1803 / 1813

页数：13

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