Safety and Efficacy of Blinatumomab in Combination With a Tyrosine Kinase Inhibitor for the Treatment of Relapsed Philadelphia Chromosome-positive Leukemia
Safety and Efficacy of Blinatumomab in Combination With a Tyrosine Kinase Inhibitor for the Treatment of Relapsed Philadelphia Chromosome-positive Leukemia
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DOI：
10.1016/j.clml.2017.08.101
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发表时间：
2017-12-01
影响因子：
2.7
通讯作者：
Jabbour, Elias
中科院分区：
文献类型：
--
作者：
Assi, Rita;Kantarjian, Hagop;Jabbour, Elias
复发难治性费城染色体阳性急性白血病患者的预后被认为是差的。Blinatumomab与TKI联合治疗导致13例患者的总体缓解率较高。这些结果是有前途的，这种策略可以尽量减少使用化疗在这种setting.Objective：费城染色体阳性（Ph+）急性淋巴细胞白血病的治疗已经彻底改变了酪氨酸激酶抑制剂（TKIs）的引入和这些药物与化疗的组合。Blinatumomab是一种双特异性抗CD 3/CD 19单克隆抗体，在复发性疾病中具有单药临床活性，与BCR-ABL 1突变状态（包括T315 I）无关。Blinatumomab联合TKI可进一步改善该高危人群的结局，包括更高的微小残留病根除率和最大限度减少化疗的使用。患者和方法：我们回顾性研究了12例复发性/难治性Ph-急性淋巴细胞白血病（n = 9）和慢性髓细胞白血病急变期（n = 3）成人患者，接受了Blinatumomab和TKI联合治疗（泊那替尼，n = 8;达沙替尼，n = 3;博舒替尼，n = 1）。所有患者既往至少接受过一线化疗失败，包括同种异体干细胞移植和1类TKI。患者接受了明显的血液学复发（n = 6）或其他方案后的持续性微小残留疾病（n = 6）治疗。结果：血液学、细胞遗传学和分子生物学完全缓解率分别为50%（3/6）、71%（5/7）和75%（9/12）。观察到2例2级细胞因子释放综合征，所有病例均在类固醇和托珠单抗治疗后消退。未发生心血管不良事件。中位随访时间为8个月，未达到中位生存期; 6个月和1年总生存率为73%。结论：Blinatumomab联合TKI治疗复发性/难治性Ph疾病患者安全有效。前瞻性研究是必要的。
The prognosis of patients with relapsed refractory Philadelphia chromosome-positive acute leukemia is considered poor. The combination of blinatumomab and a TKI resulted in high overall response rates among 13 patients. These results are promising and this strategy may minimize the use of chemotherapy in this setting.Objective: The treatment of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia has been revolutionized with the introduction of tyrosine kinase inhibitors (TKIs) and the combination of these agents with chemotherapy. Blinatumomab is a bispecific anti-CD3/CD19 monoclonal antibody with clinical activity as single-agent in the relapsed setting and independent of BCR-ABL1 mutational status, including T315I. The combination of blinatumomab with a TKI may further improve outcomes for this high-risk population, including higher eradication of minimal residual disease and minimize the use of chemotherapy. Patients and Methods: We retrospectively studied 12 adults with relapsed/refractory Ph-acute lymphoblastic leukemia (n = 9) and chronic myeloid leukemia in blast crisis (n = 3), treated with the combination blinatumomab and a TKI (ponatinib, n = 8; dasatinib, n = 3; bosutinib, n = 1). All patients have previously failed at least 1 line of chemotherapy, including allogeneic stem cell transplantation, and 1 class of TKIs. Patients were treated for either overt hematologic relapse (n = 6) or persistent minimal residual disease following other regimens (n = 6). Results: The complete hematologic, cytogenetic, and molecular response rates were 50% (3/6), 71 % (5/7), and 75% (9/12), respectively. Two cases of grade 2 cytokine release syndrome were observed, all of which resolved with steroids and tocilizumab. No cardiovascular adverse events were encountered. With a median follow-up of 8 months, the median survival was not reached; the 6-month and 1-year overall survival rates were 73%. Conclusions: The combination of blinatumomab with TKI is safe and effective in patients with relapsed/refractory Ph-disease. Prospective studies are warranted.