Combination treatment of an IDH1 inhibitor with chemotherapy in IDH1 mutant acute myeloid leukemia
Combination treatment of an IDH1 inhibitor with chemotherapy in IDH1 mutant acute myeloid leukemia
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IDH1抑制剂与化疗联合治疗IDH1突变型急性髓系白血病
DOI：
10.1007/s00277-020-04001-w
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发表时间：
2020
影响因子：
3.5
通讯作者：
Heuser M
中科院分区：
文献类型：
--
作者：
Gupta C;Kaulfuss S;Görlich K;Othman B;Chaturvedi A;Heuser M
尊敬的编辑，第一个临床IDH 1抑制剂ivosidenib作为IDH 1突变复发或难治性急性髓系白血病（AML）的单药治疗，总体缓解率为41.6%，完全缓解率为21.6%，中位缓解持续时间为8.2个月[1]。虽然这些结果在这种难以治疗的患者环境中是有希望的，但它们也表明mIDH 1抑制剂应与其他药物联合使用以提高疗效。IDH 1突变在接受标准诱导和巩固治疗的AML患者中未显示出明确的预后影响[2-5]。目前还不清楚IDH 1抑制剂如何与标准化疗联合作用，以及治疗顺序如何影响治疗效果。我们在先前报道的IDH 1突变PDX小鼠模型中评估了mIDH 1抑制剂BAY 1436032与阿糖胞苷加多柔比星序贯或同时联合治疗[6]（图1a）。用BAY 1436032治疗的所有治疗组接受药物87天（图1a）。虽然在开始治疗后第8周在媒介物治疗的小鼠中和在开始治疗后第12周在化疗治疗的小鼠中人白血病细胞的植入增加，但是在BAY 1436032治疗的小鼠中和在接受化疗的组中白血病细胞的百分比降低。
Dear Editor, The first clinical IDH1 inhibitor ivosidenib as a single agent in IDH1-mutated relapsed or refractory acute myeloid leukemia (AML) showed an overall response rate of 41.6% and a complete remission rate of 21.6% with a median duration of response of 8.2 months [1]. While these results are promising in this difficult to treat patient setting, they also suggest that mIDH1 inhibitors should be combined with other agents to improve efficacy. IDH1 mutations do not show a clear prognostic effect in AML patients who are treated with standard induction and consolidation therapy [2–5]. It is unclear how an IDH1 inhibitor acts in combination with standard chemotherapy and how the treatment sequence may affect treatment efficacy.We evaluated the mIDH1 inhibitor BAY1436032 in sequential or simultaneous combination with cytarabine plus doxorubicin in a previously reported IDH1 mutant PDX mouse model [6](Fig. 1a). All treatment groups that were treated with BAY1436032 received the drug for 87 days (Fig. 1a). While the engraftment of human leukemic cells increased in the vehicle-treated mice at week 8 and in chemotherapy-treated mice at week 12 after the start of treatment, the percentage of leukemic cells decreased in BAY1436032-treated mice as well as in the groups receiving
影响因子：
11.4
作者：
Chaturvedi, Anuhar;Goparaju, Ramya;Heuser, Michael
通讯作者：
Heuser, Michael
影响因子：
45.3
作者：
Marcucci, Guido;Maharry, Kati;Bloomfield, Clara D.
通讯作者：
Bloomfield, Clara D.