Survival impact of glucose-6-phosphate dehydrogenase deficiency in AML treated with venetoclax and azacitidine

Glucose-6-phosphate dehydrogenase (G6PD) deficiency impairs cellular redox balance and is the most common enzymatic disorder-causing anemia. Venetoclax combined with azacitidine (Ven-Aza) targets leukemic cells by disrupting oxidative phosphorylation and inducing mitochondrial stress. A study at Rabin Medical Center (Petah-Tikva, Israel) investigated the association of G6PD deficiency with overall survival of AML patients treated with Ven-Aza. Among 73 consecutive patients receiving Ven-Aza for newly diagnosed AML, 47 had normal, 11 borderline, and 15 deficient G6PD activity. Complete remission rates were 93% in the G6PD deficient group versus 69% in the normal/borderline group (p-0.03). The median overall survival was 23.8 months (95% CI 8.9-38-7) in the G6PD deficient group compared with 8.96 months (2.9-15.0) in the mormal/borderline group (p=0.034). In multivariate analysis, G6PD-deficiency was associated with improved survival as compared to normal G6PD activity (HR 0.417; p=0.043). No significant differences were observed across groups in rates of febrile neutropenia, pneumonia, sepsis, or grade 3-4 cytopenia. The authors conclude that these findings support G6PD deficiency as a potential biomarker of therapeutic sensitivity of AML to Ven-Aza.