Enasidenib mutant-IDH2复发或难治性急性髓系白血病。

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斯坦EM, DiNardo CD, Pollyea哒,Fathi, Roboz GJ,奥特曼JK,石头RM,迪安杰罗DJ,莱文RL, Flinn信息战,Kantarjian嗯,柯林斯R, Patel先生,Frankel AE,斯坦,Sekeres妈,剑RT,公元前Medeiros Willekens C, Vyas以及P, Tosolini,徐问,骑士RD,日圆KE, Agresta年代,德波顿,Tallman女士

Enasidenib mutant-IDH2复发或难治性急性髓系白血病。

血。2017年6月6日。pii:血液- 2017 - 04 - 779405。doi: 10.1182 / - 2017 - 04 - 779405血。

PubMed ID

28588020 (在PubMed

]

文摘

复发性突变异柠檬酸脱氢酶2 (IDH2)发生在~ 12%的急性髓系白血病(AML)患者。突变IDH2 neomorphically蛋白质合成2-hydroxyglutarate导致DNA和组蛋白甲基化,导致了细胞分化。Enasidenib (ag - 221 / cc - 90007)是一个first-in-class,口服,mutant-IDH2酶的选择性抑制剂。这个first-in-human, 1/2期研究评估的最大耐受剂量(MTD)、药代动力学和药效学资料、安全、和临床活动的enasidenib mutant-IDH2先进的髓系恶性血液病患者。我们为所有患者安全评估结果(N = 239)和临床疗效在最大的患者群,复发或难治性AML (N = 176),从第一阶段研究的剂量和扩张阶段。在剂量递增阶段,MTD在剂量没有达到从50 - 650毫克每天。Enasidenib 100毫克每日被选为扩张阶段基于药代动力学和药效学概要文件和证明效力。3 - 4年级enasidenib-related不良事件包括间接高胆红素血(12%)和IDH-inhibitor-associated分化综合征(IDH-DS;7%)。患者复发或难治性AML,总体响应率为40.3%,平均响应时间为5.8个月。 Responses were associated with cellular differentiation and maturation, typically without evidence of aplasia. Median overall survival among relapsed/refractory patients was 9.3 months, and for the 34 patients (19.3%) who attained complete remission was 19.7 months. Continuous daily enasidenib treatment was generally well-tolerated and induced hematologic responses in patients who had failed prior AML therapy. Inducing differentiation of myeloblasts, not cytotoxicity, appears to drive the clinical efficacy of enasidenib.

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药物

Enasidenib