Blinatumomab for minimal residual disease in adults with B-cell precursor acute lymphoblastic leukemia
Blinatumomab for minimal residual disease in adults with B-cell precursor acute lymphoblastic leukemia
复制标题
DOI：
10.1182/blood-2017-08-798322
复制
发表时间：
2018-04-05
期刊：
影响因子：
20.3
通讯作者：
Bargou, Ralf C.
中科院分区：
文献类型：
--
作者：
Goekbuget, Nicola;Dombret, Herve;Bargou, Ralf C.
大约30%-50%的急性淋巴细胞白血病（ALL）成人患者在多药治疗后血液学完全缓解，通过逆转录聚合酶链反应或流式细胞术显示微小残留病（MRD）。MRD是ALL复发的最强预测因子。在这项开放标签、单组研究中，血液学完全缓解伴MRD（>= 10（-3））的前体B细胞ALL成人患者接受Blinatumomab 15 μ g/m2/d连续IV输注，最多4个周期。患者可以在第1周期后的任何时间进行异基因造血干细胞移植。主要终点为Blinatumomab治疗1个周期后的MRD完全缓解状态。116例患者接受了Blinatumomab治疗。113例可评价患者中有88例（78%）实现了完全MRD缓解。在110例血液学缓解的Ph阴性ALL患者亚组中，Kaplan-Meier估计的18个月无复发生存率（RFS）为54%。中位总生存期（OS）为36.5个月。在里程碑分析中，与MRD无应答者相比，MRD完全应答者的RFS（23.6 vs 5.7个月; P = 0.002）和OS（38.9 vs 12.5个月; P = 0.002）更长。不良事件与既往Blinatumomab研究一致。分别有12例（10%）和3例（3%）患者发生3级或4级神经系统事件。4例患者（3%）发生细胞因子释放综合征1级，n = 2; 3级，n = 2），均发生在第1周期。在MRD阳性前体B细胞ALL患者人群中接受Blinatumomab治疗后，大多数患者实现了MRD完全缓解，与MRD无缓解者相比，RFS和OS显著延长。
Approximately 30% to 50% of adults with acute lymphoblastic leukemia (ALL) in hematologic complete remission aftermultiagent therapy exhibit minimal residual disease (MRD) by reverse transcriptase-polymerase chain reaction or flow cytometry. MRD is the strongest predictor of relapse in ALL. In this open-label, single-arm study, adults with B-cell precursor ALL in hematologic complete remission with MRD (>= 10(-3)) received blinatumomab 15 mu g/m(2) per day by continuous IV infusion for up to 4 cycles. Patients could undergo allogeneic hematopoietic stem-cell transplantation any time after cycle 1. The primary end point was complete MRD response status after 1 cycle of blinatumomab. One hundred sixteen patients received blinatumomab. Eighty-eight (78%) of 113 evaluable patients achieved a complete MRD response. In the subgroup of 110 patients with Ph-negative ALL in hematologic remission, the Kaplan-Meier estimate of relapse-free survival (RFS) at 18 months was 54%. Median overall survival (OS) was 36.5 months. In landmark analyses, complete MRD responders had longer RFS (23.6 vs 5.7 months; P = .002) and OS (38.9 vs 12.5 months; P = .002) compared with MRD nonresponders. Adverse events were consistent with previous studies of blinatumomab. Twelve (10%) and 3 patients (3%) had grade 3 or 4 neurologic events, respectively. Four patients (3%) had cytokine release syndrome grade 1, n = 2; grade 3, n = 2), all during cycle 1. After treatment with blinatumomab in a population of patients with MRD-positive B-cell precursor ALL, a majority achieved a complete MRD response, which was associated with significantly longer RFS and OS compared with MRD nonresponders.