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

Area of Science:

• Oncology
• Pharmacology
• Hematology

Background:

• Venetoclax plus hypomethylating agents (HMAs) is standard AML treatment for patients ineligible for intensive chemotherapy.
• High venetoclax cost limits accessibility in low- and middle-income countries.
• Investigating cost-reduction strategies is crucial for broader AML patient access.

Purpose of the Study:

• To evaluate the efficacy and safety of grapefruit juice with low-dose venetoclax and azacitidine.
• To assess this combination as a feasible cost-reduction strategy for AML treatment.
• To compare this regimen against standard-dose venetoclax and azacitidine.

Main Methods:

• Prospective single-center study of 44 newly diagnosed AML patients (elderly/unfit).
• Cohort 1 (n=34): Standard-dose venetoclax + azacitidine.
• Cohort 2 (n=10): Low-dose venetoclax + grapefruit juice + azacitidine.
• Evaluated response rates, overall survival (OS), progression-free survival (PFS), venetoclax Cmax, and adverse events.

Main Results:

• Overall response rates (ORR) were 91.2% (Cohort 1) and 100% (Cohort 2).
• Median OS was 9 months (Cohort 1) vs. 8.15 months (Cohort 2).
• Median PFS was 7 months (Cohort 1) vs. 6.15 months (Cohort 2).
• No significant difference in venetoclax Cmax or survival outcomes between cohorts.
• Common adverse events included thrombocytopenia, anemia, and neutropenia.

Conclusions:

• Low-dose venetoclax with grapefruit juice offers comparable efficacy and safety to standard-dose venetoclax.
• This combination achieves a 75% reduction in drug costs.
• Presents a cost-effective option for AML patients in resource-limited settings.
• Further large-scale, multicenter studies are needed to validate this regimen.