Immunopharmacologic response of patients with B-lineage acute lymphoblastic leukemia to continuous infusion of T cell-engaging CD19/CD3-bispecific BiTE antibody blinatumomab
Immunopharmacologic response of patients with B-lineage acute lymphoblastic leukemia to continuous infusion of T cell-engaging CD19/CD3-bispecific BiTE antibody blinatumomab
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DOI：
10.1182/blood-2012-01-400515
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发表时间：
2012-06-28
期刊：
影响因子：
20.3
通讯作者：
Kufer, Peter
中科院分区：
文献类型：
--
作者：
Klinger, Matthias;Brandl, Christian;Kufer, Peter
在极少量残留B系急性淋巴细胞白血病（MRD+ B-ALL）患者中，结合T细胞的CD 19/CD 3双特异性BiTE Ab Blinatumomab显示出80%的完全分子学缓解率和延长的无白血病生存期。在此，我们报告了一项II期研究中所有患者的淋巴细胞对Blinatumomab持续输注的反应方式惊人相似。开始输注后，B细胞计数平均在2天内降至< 1 B细胞/μ L，并且在整个治疗期间基本上保持不可检测。相比之下，所有患者的T细胞计数在< 1天内下降到最低点，并在几天内恢复到基线。然后，在持续输注Blinatumomab的2-3周内，T细胞扩增，平均比基线增加一倍以上。显著百分比的重新出现的CD 8（+）和CD 4（+）T细胞新表达活化标记物CD 69。输注开始后不久，观察到以IL-10、IL-6和IFN-γ为主的细胞因子的短暂释放，在第二个治疗周期开始时不再发生。白血病患者淋巴细胞对Blinatumomab持续输注的反应有助于更好地了解这种抗体和其他全局T细胞结合抗体的作用方式。该试验注册于www.clinicaltrials.gov，标识符为NCT 00560794。（血。2012;119（26）：6226-6233）
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)