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依尼舒尼对比传统治疗用于治疗 IDH2 突变晚期复发/难治性 AML 老年患者:一项随机 3 期临床试验。

Enasidenib vs conventional care in older patients with late-stage mutant-IDH2 relapsed/refractory AML: a randomized phase 3 trial.

机构信息

Gustave Roussy, Université Paris-Saclay, Villejeuf, France.

Hospital Universitari i Politecnic La Fe, Valencia, Spain.

出版信息

Blood. 2023 Jan 12;141(2):156-167. doi: 10.1182/blood.2021014901.

Abstract

This open-label, randomized, phase 3 trial (NCT02577406) compared enasidenib, an oral IDH2 (isocitrate dehydrogenase 2) inhibitor, with conventional care regimens (CCRs) in patients aged ≥60 years with late-stage, mutant-IDH2 acute myeloid leukemia (AML) relapsed/refractory (R/R) to 2 or 3 prior AML-directed therapies. Patients were first preselected to a CCR (azacitidine, intermediate-dose cytarabine, low-dose cytarabine, or supportive care) and then randomized (1:1) to enasidenib 100 mg per day or CCR. The primary endpoint was overall survival (OS). Secondary endpoints included event-free survival (EFS), time to treatment failure (TTF), overall response rate (ORR), hematologic improvement (HI), and transfusion independence (TI). Overall, 319 patients were randomized to enasidenib (n = 158) or CCR (n = 161). The median age was 71 years, median (range) enasidenib exposure was 142 days (3 to 1270), and CCR was 36 days (1 to 1166). One enasidenib (0.6%) and 20 CCR (12%) patients received no randomized treatment, and 30% and 43%, respectively, received subsequent AML-directed therapies during follow-up. The median OS with enasidenib vs CCR was 6.5 vs 6.2 months (HR [hazard ratio], 0.86; P = .23); 1-year survival was 37.5% vs 26.1%. Enasidenib meaningfully improved EFS (median, 4.9 vs 2.6 months with CCR; HR, 0.68; P = .008), TTF (median, 4.9 vs 1.9 months; HR, 0.53; P < .001), ORR (40.5% vs 9.9%; P <.001), HI (42.4% vs 11.2%), and red blood cell (RBC)-TI (31.7% vs 9.3%). Enasidenib safety was consistent with prior reports. The primary study endpoint was not met, but OS was confounded by early dropout and subsequent AML-directed therapies. Enasidenib provided meaningful benefits in EFS, TTF, ORR, HI, and RBC-TI in this heavily pretreated older mutant-IDH2 R/R AML population.

摘要

这项开放标签、随机、3 期试验(NCT02577406)比较了enasidenib(一种口服 IDH2(异柠檬酸脱氢酶 2)抑制剂)与常规治疗方案(CCR)在 2 或 3 种先前 AML 靶向治疗后复发/难治性(R/R)的年龄≥60 岁晚期突变 IDH2 急性髓系白血病(AML)患者中的疗效。患者首先被预先选择接受 CCR(阿扎胞苷、中剂量阿糖胞苷、低剂量阿糖胞苷或支持性护理),然后随机(1:1)接受 enasidenib 每天 100 mg 或 CCR。主要终点是总生存期(OS)。次要终点包括无事件生存期(EFS)、治疗失败时间(TTF)、总缓解率(ORR)、血液学改善(HI)和输血独立性(TI)。共有 319 名患者被随机分配至enasidenib(n=158)或 CCR(n=161)。中位年龄为 71 岁,中位(范围)enasidenib 暴露时间为 142 天(3 至 1270),CCR 为 36 天(1 至 1166)。1 名 enasidenib(0.6%)和 20 名 CCR(12%)患者未接受随机治疗,分别有 30%和 43%的患者在随访期间接受了随后的 AML 靶向治疗。与 CCR 相比,enasidenib 的中位 OS 为 6.5 个月 vs 6.2 个月(HR[风险比],0.86;P=0.23);1 年生存率为 37.5% vs 26.1%。Enasidenib 显著改善了 EFS(中位值,4.9 个月 vs CCR 的 2.6 个月;HR,0.68;P=0.008)、TTF(中位值,4.9 个月 vs 1.9 个月;HR,0.53;P<0.001)、ORR(40.5% vs 9.9%;P<0.001)、HI(42.4% vs 11.2%)和红细胞(RBC)-TI(31.7% vs 9.3%)。Enasidenib 的安全性与先前的报告一致。主要研究终点未达到,但 OS 受到早期失访和随后的 AML 靶向治疗的影响。在这一接受过多线预处理的老年突变 IDH2 R/R AML 人群中,enasidenib 在 EFS、TTF、ORR、HI 和 RBC-TI 方面提供了有意义的获益。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3920/10644040/3bfce756d90d/BLOOD_BLD-2021-014901-fx1.jpg

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