Immunopharmacologic response of patients with B-lineage acute lymphoblastic leukemia to continuous infusion of T cell-engaging CD19/CD3-bispecific BiTE antibody blinatumomab

被引：386

作者：

Klinger, Matthias ^{[1
]}

Brandl, Christian ^{[1
]}

Zugmaier, Gerhard ^{[1
]}

Hijazi, Youssef ^{[1
]}

Bargou, Ralf C. ^{[2
]}

Topp, Max S. ^{[2
]}

Goekbuget, Nicola ^{[3
]}

Neumann, Svenja ^{[4
]}

Goebeler, Mariele ^{[2
]}

Viardot, Andreas ^{[5
]}

Stelljes, Matthias ^{[6
]}

Brueggemann, Monika ^{[4
]}

Hoelzer, Dieter ^{[3
]}

Degenhard, Evelyn ^{[1
]}

Nagorsen, Dirk ^{[1
]}

Baeuerle, Patrick A. ^{[1
]}

Wolf, Andreas ^{[1
]}

Kufer, Peter ^{[1
]}

机构：

[1] Amgen Res Munich GmbH, D-81477 Munich, Germany

[2] Univ Klinikum Wurzburg, Med Klin & Poliklin 2, Wurzburg, Germany

[3] Johann Wolfgang Goethe Univ Klinikum, Med Klin 2, Frankfurt, Germany

[4] Univ Klinikum Schleswig Holstein, Med Klin & Poliklin 2, Kiel, Germany

[5] Univ Ulm Klinikum, Innere Med Klin 3, Ulm, Germany

[6] Univ Klinikum Munster, Med Klin A, Munster, Germany

来源：

BLOOD | 2012年 / 119卷 / 26期

关键词：

SINGLE-CHAIN ANTIBODY; MINIMAL RESIDUAL DISEASE; THERAPY; CANCER; CONSTRUCTS; ACTIVATION; MELANOMA; POTENT;

D O I：

10.1182/blood-2012-01-400515

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

T cell-engaging CD19/CD3-bispecific BiTE Ab blinatumomab has shown an 80% complete molecular response rate and prolonged leukemia-free survival in patients with minimal residual B-lineage acute lymphoblastic leukemia (MRD+ B-ALL). Here, we report that lymphocytes in all patients of a phase 2 study responded to continuous infusion of blinatumomab in a strikingly similar fashion. After start of infusion, B-cell counts dropped to < 1 B cell/mu L within an aver-age of 2 days and remained essentially undetectable for the entire treatment period. By contrast, T-cell counts in all patients declined to a nadir within < 1 day and recovered to baseline within a few days. T cells then expanded and on average more than doubled over baseline within 2-3 weeks under continued infusion of blinatumomab. A significant percentage of reappearing CD8(+) and CD4(+) T cells newly expressed activation marker CD69. Shortly after start of infusion, a transient release of cytokines dominated by IL-10, IL-6, and IFN-gamma was observed, which no longer occurred on start of a second treatment cycle. The response of lymphocytes in leukemic patients to continuous infusion of blinatumomab helps to better understand the mode of action of this and other globally T cell-engaging Abs. The trial is registered with www.clinicaltrials.gov identifier NCT00560794. (Blood. 2012;119(26):6226-6233)

引用

页码：6226 / 6233

页数：8

共 31 条

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