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Abstract：
Adult patients with relapsed/refractory (R/R) B-precursor acute lymphoblastic leukemia (ALL) have a poor prognosis. Blinatumomab is a bispecific T-cell engager (BiTE) immuno-oncology therapy with dual specificity for CD19 and CD3 that redirects patients\' CD3-positive cytotoxic T cells to lyse malignant and normal B cells. We conducted an open-label, phase 1b/2 study to determine the safety, pharmacokinetics, efficacy and recommended dose of blinatumomab in Japanese adults with R/R B-precursor ALL. Patients received 9 μg/day blinatumomab during week 1 and 28 μg/day during weeks 2-4, with a 2-week treatment-free interval (6-week cycle); patients received 28 μg/day blinatumomab in subsequent cycles. Primary endpoints were the incidence of dose-limiting toxicities (DLT) in phase 1b and complete remission (CR)/CR with partial hematologic recovery (CRh) within the first two cycles in phase 2. A total of 26 patients enrolled and 25 (96%) reported grade ≥3 adverse events (mostly cytopenias). There were no DLT. CR/CRh within two cycles was achieved by 4 of 5 patients (80%) in phase 1b and 8 of 21 patients (38%) in phase 2. Among patients with evaluable minimal residual disease, 4 (100%) in phase 1b and 3 (38%) in phase 2 had a complete MRD response. Median RFS for 8 patients who achieved CR/CRh in phase 2 was 5 (95% CI: 3.5-6.4) months; median OS was not estimable. There were no significant associations between maximum cytokine levels or percentage of specific cell types during cycle 1 and response. Consistent with global studies, blinatumomab appeared to be safe and efficacious in Japanese adults with R/R ALL.
摘要：
患有复发/难治性（R/R）B前体急性淋巴细胞白血病（ALL）的成年患者预后不良。Blinatumomab是一种双特异性T细胞衔接剂（BiTE）免疫肿瘤学疗法，对CD19和CD3具有双重特异性，可重定向患者CD3阳性细胞毒性T细胞以裂解恶性和正常B细胞。我们进行了一个开放标签，1b/2阶段研究以确定安全性，药代动力学，Blinatumomab在日本成人R/RB前体ALL中的疗效和推荐剂量。患者在第1周接受9μg/天的blinatumomab，在第2-4周接受28μg/天的blinatumomab，无2周治疗间隔（6周周期）；患者在随后的周期中接受28μg/天的blinatumomab。主要终点是1b期剂量限制性毒性（DLT）的发生率和2期前两个周期内完全缓解（CR）/部分血液学恢复（CRh）的CR。共纳入26例患者，其中25例（96%）报告了≥3级不良事件（主要是血细胞减少症）。没有DLT。在两个周期内的CR/CRh在1b期中由5名患者中的4名（80％）和在2期中由21名患者中的8名（38％）实现。在可评估的微小残留病的患者中，阶段1b中的4（100％）和阶段2中的3（38％）具有完整的MRD响应。在2期达到CR/CRh的8例患者的中位RFS为5个月（95％CI：3.5-6.4）；中位OS不可估计。在第1周期期间的最大细胞因子水平或特定细胞类型的百分比与反应之间没有显着关联。与全球研究一致，在患有R/RALL的日本成年人中，blinatumomab似乎是安全有效的。
