Effect of oral posaconazole on venetoclax plasma concentration and efficacy in patients with acute myeloid leukemia

Abstract

BCL-2 was the first gene identified to have antiapoptotic effects and venetoclax is an oral selective BCL-2 inhibitor, which has great potential in the treatment of patients with acute myeloid leukemia (AML) who are not candidates for intensive therapy. Notably, posaconazole, an oral antifungal drug, is also a strong factor that can affect blood venetoclax concentrations. To the best of our knowledge, the relationship between BCL-2 expression, posaconazole and venetoclax, as well as the influence of them on treatment efficacy and the prognosis of patients with AML, has not been reported. Therefore, in the present study, the relationship between BCL-2 expression and blood venetoclax concentration was analyzed in 35 patients with AML. BCL-2 mRNA expression levels were examined by reverse transcription quantitative PCR. Blood venetoclax concentrations were measured using high-performance liquid chromatography-tandem mass spectrometry. The results revealed that among patients with AML, those with lower primary BCL-2 expression had a higher complete remission (CR) rate (P = 0.005), overall response rate (P < 0.0001) and progression-free survival time (P = 0.04). Posaconazole was revealed to be a strong factor that was able to increase blood venetoclax concentration (P < 0.001) and CR rate in the venetoclax plus posaconazole group compared with that in the venetoclax monotherapy group (P = 0.002); however, no significant difference was identified in the occurrence of adverse reactions between these groups. Among low and high blood venetoclax concentration groups, the event-free survival of the former group was significantly higher (P = 0.013). In conclusion, the results of the present study could be used to guide clinical practice in the treatment of AML.