Pharmacology-Guided venetoclax dose reduction with azacitidine in older or unfit acute myeloid leukemia: A North African experience from a Moroccan single-center cohort and exploratory hospital cost-effectiveness analysis

Abstract

Introduction

Azacitidine-venetoclax has improved outcomes in older or intensive chemotherapy-ineligible acute myeloid leukemia (AML) patients. However, real-world experience and pharmacoeconomic evidence remain scarce in resource-limited settings, particularly in North Africa, where drug pricing and supportive care constraints significantly shape clinical practice.

Methods

A retrospective single-center study was conducted at a tertiary military teaching hospital in Morocco (December 2019–December 2025). Fifteen older or unfit AML patients receiving azacitidine-based regimens were included. Venetoclax was dose-reduced to 100 mg/day under concomitant voriconazole prophylaxis based on CYP3A4 inhibition principles. Kaplan-Meier survival analysis was performed. An exploratory pharmacoeconomic analysis was conducted from a hospital perspective, incorporating drug acquisition costs, infection-related hospitalization expenses, and quality-adjusted life-years (QALYs) derived from the literature.

Results

Complete remission was achieved in 78% of first-line azacitidine-venetoclax recipients (n = 9) and 50% with azacitidine alone (n = 4). Infectious complications occurred in 73.3% of patients. Median overall survival was not reached; estimated survival probabilities were 76% at 12 months and 57% at 24 months. The incremental cost-effectiveness ratio (ICER) of azacitidine-venetoclax versus azacitidine alone was approximately 183,000 MAD per QALY gained (≈2× Morocco's GDP per capita) after incorporating infection-related costs. Venetoclax acquisition price was the primary cost-effectiveness driver on sensitivity analysis.

Conclusions

Pharmacology-guided azacitidine-venetoclax regimens are clinically feasible in resource-limited settings, with encouraging survival outcomes. Infection management, antifungal prophylaxis strategies, and targeted drug pricing negotiations are key determinants of cost-effectiveness. Prospective multicenter studies are warranted.