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.

中文翻译：

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Enasidenib 与常规治疗对晚期 IDH2 突变型复发/难治性 AML 老年患者的治疗：一项随机 3 期试验。

这项开放标签、随机、3 期试验 (NCT02577406) 在年龄≥60 岁的晚期 IDH2 突变急性髓性白血病患者中比较了 enasidenib（一种口服 IDH2（异柠檬酸脱氢酶 2）抑制剂）与常规护理方案 (CCR) (AML) 先前接受过 2 种或 3 种 AML 定向治疗后出现复发/难治性 (R/R)。患者首先被预选接受 CCR（阿扎胞苷、中剂量阿糖胞苷、低剂量阿糖胞苷或支持治疗），然后随机 (1:1) 接受每天 100 mg 的enasidenib 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）、总体缓解率（ORR）、血液学改善（HI）和输血独立性（TI）。总体而言，319 名患者被随机分配接受enasidenib (n = 158) 或 CCR (n = 161) 治疗。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% 在随访期间接受了后续针对AML 的治疗。enasidenib 与 CCR 的中位 OS 分别为 6.5 个月和 6.2 个月（HR [风险比]，0.86；P = .23）；1 年生存率为 37.5% vs 26.1%。Enasidenib 显着改善了 EFS（中位 CCR 为 4.9 个月与 2.6 个月；HR，0.68；P = .008）、TTF（中位为 4.9 个月与 1.9 个月；HR，0.53；P < .001）、ORR（40.5% 与 9.9%） ; P <.001)、HI (42.4% vs 11.2%) 和红细胞 (RBC)-TI (31.7% vs 9.3%)。Enasidenib 的安全性与之前的报告一致。主要研究终点并未达到，但早期退出和随后的 AML 定向治疗使 OS 受到影响。Enasidenib 在这个经过大量预处理的老年突变 IDH2 R/R AML 群体中，在 EFS、TTF、ORR、HI 和 RBC-TI 方面提供了有意义的益处。