Devimistat plus chemotherapy vs chemotherapy alone for older relapsed or refractory patients with AML: results of the ARMADA trial

Blood Neoplasia Pub Date : 2024-03-29 DOI:10.1016/j.bneo.2024.100009

Timothy S. Pardee , Bayard L. Powell , Richard A. Larson , Joseph Maly , Michael Keng , Matthew Foster , Eun-Ji Choi , Heinz Sill , Thomas Cluzeau , Deepa Jeyakumar , Olga Frankfurt , Prapti Patel , Michael Schuster , Elisabeth Koller , Regis Costello , Uwe Platzbecker , Pau Montesinos , Susana Vives , Aziz Nazha , Rachel Cook , Jorge Cortes

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Abstract

Acute myeloid leukemia (AML) is an aggressive cancer of the myeloid lineage. Outcomes in older patients are poor, with high rates of resistant and relapsed disease. Devimistat is a lipoic acid analog that inhibits mitochondrial metabolism. Devimistat combined with high-dose cytarabine and mitoxantrone resulted in promising phase 1 and 2 response rates especially in older patients. Therefore, the phase 3 ARMADA 2000 trial was conducted in patients aged ≥50 years with relapsed or refractory AML. The study randomized patients between devimistat combined with high-dose cytarabine and mitoxantrone (CHAM) or 1 of 3 control treatment regimens without devimistat: high-dose cytarabine and mitoxantrone; mitoxantrone, etoposide, and cytarabine; or fludarabine, cytarabine, and filgrastim. Overall, 265 patients consented to participate from 56 sites across 11 countries, and 200 patients were randomized, 98 patients to the devimistat arm and 102 patients to the control arm. The safety profile was consistent with high-dose cytarabine–based salvage regimens. There were 18 (9%) deaths on study (11 on CHAM and 7 on control). The study failed to meet its primary end point, with a complete remission (CR) rate of 20.4% in the devimistat arm compared with 21.6% in the control arm (P = .57). Overall survival was not statistically significantly different between the study arms, with a median of 8.9 months in the CHAM arm compared with 6.2 months in the control arm (P = .62). In conclusion, devimistat added to chemotherapy did not improve the CR rate or survival in patients aged ≥50 years with relapsed or refractory AML. This trial was registered at www.ClinicalTrials.gov as #NCT03504410.

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复发或难治性急性髓细胞白血病老年患者Devimistat联合强化化疗与单独强化化疗的对比：随机III期ARMADA试验结果

摘要急性髓性白血病（AML）是一种侵袭性髓系癌症。老年患者的治疗效果很差，耐药和复发率很高。Devimistat是一种硫辛酸类似物，可抑制线粒体代谢。Devimistat 与大剂量阿糖胞苷和米托蒽醌联用后，第一和第二阶段的应答率很高，尤其是在老年患者中。因此，ARMADA 2000 第三期试验在年龄≥50 岁的复发或难治性急性髓细胞白血病患者中进行。该研究将患者随机分为两种治疗方案，一种是 devimistat 与大剂量阿糖胞苷和米托蒽醌联合治疗（CHAM），另一种是不使用 devimistat 的 3 种对照治疗方案中的一种：大剂量阿糖胞苷和米托蒽醌；米托蒽醌、依托泊苷和阿糖胞苷；或氟达拉滨、阿糖胞苷和非格司亭。共有来自11个国家56个研究机构的265名患者同意参加这项研究，200名患者被随机分配，其中98名患者被分配到devimistat治疗组，102名患者被分配到对照组。该疗法的安全性与基于大剂量阿糖胞苷的抢救方案一致。研究中出现了 18 例（9%）死亡病例（11 例死于 CHAM，7 例死于对照组）。研究未能达到主要终点，devimistat治疗组的完全缓解（CR）率为20.4%，而对照组为21.6%（P = .57）。研究臂之间的总生存期无明显统计学差异，CHAM研究臂的中位生存期为8.9个月，对照组为6.2个月（P = .62）。总之，对于年龄≥50岁的复发或难治性急性髓细胞性白血病患者，在化疗中添加 devimistat 并不能提高 CR 率或生存率。该试验已在 www.ClinicalTrials.gov 注册，注册号为 #NCT03504410。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Blood Neoplasia

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