Complete Hematologic and Molecular Response in Adult Patients With Relapsed/Refractory Philadelphia Chromosome-Positive B-Precursor Acute Lymphoblastic Leukemia Following Treatment With Blinatumomab: Results From a Phase II, Single-Arm, Multicenter Study
Complete Hematologic and Molecular Response in Adult Patients With Relapsed/Refractory Philadelphia Chromosome-Positive B-Precursor Acute Lymphoblastic Leukemia Following Treatment With Blinatumomab: Results From a Phase II, Single-Arm, Multicenter Study
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DOI：
10.1200/jco.2016.69.3531
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发表时间：
2017-06-01
影响因子：
45.3
通讯作者：
Stein, Anthony
中科院分区：
文献类型：
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作者：
Martinelli, Giovanni;Boissel, Nicolas;Stein, Anthony
目的对于以酪氨酸激酶抑制剂(TKI)为基础的治疗失败后进展的费城染色体阳性(Ph+)B前体急性淋巴细胞白血病(ALL)患者，有几种治疗方案可供选择。在这里，我们评估了blinatumomab在复发或难治性Ph+ALL患者中的疗效和耐受性。患者和方法这项开放标签II期研究纳入了Ph+ALL成年人，他们在至少一代或更晚的TKI后复发或对TKI无效，或对第二代或更晚的TKI不耐受，对伊马替尼不耐药或难治性。Blinatumomab持续静脉滴注，28天为一周期。在前两个周期中，主要终点是完全缓解(CR)或部分血液学恢复(CRH)。主要次要终点包括最小残留病反应、异基因造血干细胞移植、无复发存活率、总存活率和不良事件(AEs)。结果45例患者中，16例(36%；95%CI，22%~51%)在前两个周期中实现了CR/CRH，包括10例T315I突变患者中的4例；88%的CR/CRH应答者获得了完全的最小残留病反应。7名应答者(44%)进行了异基因造血干细胞移植，包括55%(6/11)的移植初应者。中位无复发生存期为6.7个月，总生存期为7.1个月。最常见的不良反应是发热(58%)、发热性中性粒细胞减少(40%)和头痛(31%)。3名患者有细胞因子释放综合征(均为1级或2级)，3名患者有3级神经系统事件，其中1例(失语症)需要暂时中断治疗。结论单药blinatumomab对复发或对TKIs无效的高危Ph+ALL患者具有抗白血病活性。在Ph-ALL中，AES与以前的经验一致。
PurposeFew therapeutic options are available for patients with Philadelphia chromosome-positive (Ph+) B-precursor acute lymphoblastic leukemia (ALL) who progress after failure of tyrosine kinase inhibitor (TKI) -based therapy. Here, we evaluated the efficacy and tolerability of blinatumomab in patients with relapsed or refractory Ph+ ALL.Patients and MethodsThis open-label phase II study enrolled adults with Ph+ ALL who had relapsed after or were refractory to at least one second-generation or later TKI or were intolerant to second-generation or later TKIs and intolerant or refractory to imatinib. Blinatumomab was administered in 28-day cycles by continuous intravenous infusion. The primary end point was complete remission (CR) or CR with partial hematologic recovery (CRh) during the first two cycles. Major secondary end points included minimal residual disease response, rate of allogeneic hematopoietic stem-cell transplantation, relapse-free survival, overall survival, and adverse events (AEs).ResultsOf 45 patients, 16 (36%; 95% CI, 22% to 51%) achieved CR/CRh during the first two cycles, including four of 10 patients with the T315I mutation; 88% of CR/CRh responders achieved a complete minimal residual disease response. Seven responders (44%) proceeded to allogeneic hematopoietic stem-cell transplantation, including 55% (six of 11) of transplantation-naive responders. Median relapse-free survival and overall survival were 6.7 and 7.1 months, respectively. The most frequent AEs were pyrexia (58%), febrile neutropenia (40%), and headache (31%). Three patients had cytokine release syndrome (all grade 1 or 2), and three patients had grade 3 neurologic events, one of which (aphasia) required temporary treatment interruption. There were no grade 4 or 5 neurologic events.ConclusionSingle-agent blinatumomab showed antileukemia activity in high-risk patients with Ph+ ALL who had relapsed or were refractory to TKIs. AEs were consistent with previous experience in Ph- ALL.