Safety and Efficacy of Grapefruit Juice Combined With Low-Dose Venetoclax in AML Patients Ineligible for Intensive Chemotherapy.

PURPOSE

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.

METHODS

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.

FINDINGS

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.

IMPLICATIONS

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.