Bortezomib with standard chemotherapy for children with acute myeloid leukemia does not improve treatment outcomes: a report from the Children's Group
Bortezomib with standard chemotherapy for children with acute myeloid leukemia does not improve treatment outcomes: a report from the Children's Group
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DOI：
10.3324/haematol.2019.220962
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发表时间：
2020-07-01
期刊：
影响因子：
10.1
通讯作者：
Gamis, Alan
中科院分区：
文献类型：
--
作者：
Aplenc, Richard;Meshinchi, Soheil;Gamis, Alan
儿童急性髓性白血病（AML）需要新的治疗策略来减少疾病复发和治疗相关的发病率。儿童肿瘤组III期AAML1031试验测试了在标准化疗中加入硼替佐米是否能提高新诊断AML的儿科患者的生存率。AAML1031将年龄小于30岁的新发AML患者随机分配到使用或不使用硼替佐米的标准治疗。所有患者均接受相同的化疗，包括4个强化化疗疗程，高危患者接受3个化疗疗程后再进行同种异体造血干细胞移植。对于随机分配到干预组的患者，在每个化疗疗程的第1、4和8天给予硼替佐米1.3 mg/m(2)。对于那些随机分配到对照组的患者，不给予波特佐米。总共有1097名患者被随机分配到标准化疗组（n=542）或硼替佐米标准化疗组（n=555）。硼替佐米组与对照组缓解诱导率无差异（89% vs 91%, P =0.531）。与对照组相比，硼替佐米未能改善3年无事件生存率（44.8 +/- 4.5% vs 47.0 +/- 4.5%, P = 0.236）或总生存率（63.6 +/- 4.5 vs 67.2 +/- 4.3, P =0.356）。然而，在第一个疗程中，硼替佐米明显与更多的周围神经病变（P =0.006）和重症监护病房入院（P = 0.025）相关。在标准化疗中加入硼替佐米增加了毒性，但没有改善生存。这些数据不支持将硼替佐米添加到新发AML儿童的标准化疗中。
New therapeutic strategies are needed for pediatric acute myeloid leukemia (AML) to reduce disease recurrence and treatment-related morbidity. The Children's Oncology Group Phase III AAML1031 trial tested whether the addition of bortezomib to standard chemotherapy improves survival in pediatric patients with newly diagnosed AML. AAML1031 randomized patients younger than 30 years of age with de novo AML to standard treatment with or without bortezomib. All patients received the identical chemotherapy backbone with either four intensive chemotherapy courses or three courses followed by allogeneic hematopoiet- ic stem cell transplantation for high-risk patients. For those randomized to the intervention arm, bortezomib 1.3 mg/m(2) was given on days 1, 4 and 8 of each chemotherapy course. For those randomized to the control arm, borte-zomib was not administered. In total, 1,097 patients were randomized to standard chemotherapy (n=542) or standard chemotherapy with bortezomib (n=555). There was no difference in remission induction rate between the bortezomib and control treatment arms (89% vs. 91%, P =0.531). Bortezomib failed to improve 3-year event-free survival (44.8 +/- 4.5% vs. 47.0 +/- 4.5%, P = 0.236) or overall survival (63.6 +/- 4.5 vs. 67.2 +/- 4.3, P =0.356) compared with the control arm. However, bortezomib was associated with significantly more peripheral neuropathy (P =0.006) and intensive care unit admissions (P = 0.025) during the first course. The addition of bortezomib to standard chemotherapy increased toxicity but did not improve survival. These data do not support the addition of bortezomib to standard chemotherapy in children with de novo AML.