Relationship Between BCL-2 Expression and Venetoclax Concentration Among Patients With AML
For patients with newly diagnosed with acute myeloid leukemia (AML), higher levels of BCL-2 expression may be associated with lower treatment efficacy, while higher levels of venetoclax concentration, potentially related to treatment with posaconazole, may advance the timing of adverse reactions leading to inferior event-free survival, according to study results published in Recent Patents on Anti-Cancer Drug Discovery.
BCL-2 inhibitors, such as venetoclax, have demonstrated potential for the treatment of AML due to its apoptotic effects and ability to reduce BCL-2 expression. Posaconazole, an antifungal therapy, can affect venetoclax concentration in the bloodstream, however research is limited on the effects of antifungal treatment on treatment efficacy for AML with venetoclax.
Researchers conducted a single-center, retrospective study among patients with AML (n = 35) to determine the impact of posaconazole on BCL-2 expression and venetoclax concentration. Gene expression levels and blood concentration of BCL-2 inhibitors were collected via diagnostic testing and examined. All patients received a treatment of azacitidine plus cytarabine, patients were then stratified to venetoclax monotherapy (n = 18) or venetoclax plus posaconazole (n = 17).
Patients who received combined venetoclax plus posaconazole therapy had higher levels of venetoclax blood concentrations compared to venetoclax monotherapy patients (P <. 0001). Patients with lower primary BCL-2 expression at enrollment had higher rates of complete remission (CR) rate (P = .005), overall response rate (P <.0001), and progression-free survival (PFS) time (P = .04), compared with patients who had higher levels of BCL-2 expression in either treatment group. Additionally, patients with a lower blood concentration of venetoclax were found to have longer event-free survival than those with a higher concentration (P = .013).
No differences were found in the occurrence of adverse reactions between either group. However, “Higher levels of BCL-2 expression at initial diagnosis may have adverse effects on the efficacy and prognosis of patients, and higher levels of venetoclax concentration may advance the time of adverse reactions in patients, thus adversely affecting event-free survival,” the researchers concluded.
Source:
Guo M, He Y, Du J, Qiu D, Qin Y, Huang Y. Effect of Oral Posaconazole on Venetoclax Plasma Concentration and its Efficacy in Patients with Acute Myeloid Leukemia. Recent patents on anti-cancer drug discovery. Published online January 8, 2025. doi: 10.2174/0115748928330206241104161111