Meng Danchen, Li YuXin, Ruan Min, Hou ZhengFeng, Liu Xinyao, Wu Wei, Ge Jian, Huang Zhengqi, Yang Jichun, Long Zhangbiao
Department of Hematology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
Clin Ther. 2025 Aug;47(8):595-601. doi: 10.1016/j.clinthera.2025.05.008. Epub 2025 Jun 13.
Venetoclax in combination with hypomethylating agents (HMAs) has become the standard treatment for acute myeloid leukemia (AML) patients ineligible for intensive chemotherapy. However, its high cost limits its accessibility in low- and middle-income countries. This study aims to evaluate the efficacy and safety of grapefruit juice combined with low-dose venetoclax and azacitidine as a feasible cost-reduction strategy.
This prospective single-center study included 44 newly diagnosed elderly or unfit AML patients treated at our hospital between December 2020 and May 2024. Patients were assigned to two cohorts in parallel: 34 patients received standard-dose venetoclax combined with azacitidine (cohort 1), whereas 10 patients received low-dose venetoclax combined with grapefruit juice and azacitidine (cohort 2). The response to treatment, overall survival (OS), and progression-free survival (PFS) were evaluated. The peak venetoclax concentration (C) and side effects of the patients were also monitored.
The median age of participants was 67.5 years (25 males and 19 females). The overall response rate (ORR) after the first treatment cycle was 85.3% in cohort 1 and 100% in cohort 2 (P = 0.5730), and the best ORR was 91.2% in cohort 1 and 100% in cohort 2 (P > 0.9999). The median OS was 9 months in cohort 1 and 8.15 months in cohort 2 (P = 0.7103). The median PFS was 7 months in cohort 1 and 6.15 months in cohort 2 (P = 0.7068). The median Cmax of venetoclax in the whole cohort was 1664 ng/mL, with no significant difference between groups (P = 0.1614), and no significant correlation observed between venetoclax Cmax and age (P = 0.4575). The most common adverse events were thrombocytopenia, anemia, and neutropenia.
The combination of grapefruit juice with low-dose venetoclax demonstrates comparable efficacy and safety to the standard-dose regimen, while achieving a 75% reduction in drug costs. This approach offers a cost-effective treatment option for AML patients in resource-limited settings. Further large-scale, multicenter studies are required to validate the clinical feasibility of this regimen.
维奈克拉联合低甲基化药物（HMAs）已成为不适宜接受强化化疗的急性髓系白血病（AML）患者的标准治疗方案。然而，其高昂的成本限制了在低收入和中等收入国家的可及性。本研究旨在评估葡萄柚汁联合低剂量维奈克拉和阿扎胞苷作为一种可行的成本降低策略的疗效和安全性。
这项前瞻性单中心研究纳入了2020年12月至2024年5月在我院接受治疗的44例新诊断的老年或身体状况不佳的AML患者。患者被平行分配到两个队列：34例患者接受标准剂量维奈克拉联合阿扎胞苷（队列1），而10例患者接受低剂量维奈克拉联合葡萄柚汁和阿扎胞苷（队列2）。评估治疗反应、总生存期（OS）和无进展生存期（PFS）。还监测了患者的维奈克拉峰值浓度（C）和副作用。
参与者的中位年龄为67.5岁（25例男性和19例女性）。第一个治疗周期后的总缓解率（ORR）在队列1中为85.3%，在队列2中为100%（P = 0.5730），最佳ORR在队列1中为91.2%，在队列2中为100%（P > 0.9999）。队列1的中位OS为9个月，队列2为8.15个月（P = 0.7103）。队列1的中位PFS为7个月，队列2为6.15个月（P = 0.7068）。整个队列中维奈克拉的中位Cmax为1664 ng/mL，组间无显著差异（P = 0.1614），且维奈克拉Cmax与年龄之间未观察到显著相关性（P = 0.4575）。最常见的不良事件是血小板减少、贫血和中性粒细胞减少。
葡萄柚汁联合低剂量维奈克拉显示出与标准剂量方案相当的疗效和安全性，同时药物成本降低了75%。这种方法为资源有限环境中的AML患者提供了一种具有成本效益的治疗选择。需要进一步的大规模、多中心研究来验证该方案的临床可行性。
