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image of Effect of Oral Posaconazole on Venetoclax Plasma Concentration and its Efficacy in Patients with Acute Myeloid Leukemia

Abstract

Background

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 their influence on treatment efficacy and the prognosis of patients with AML, has not been reported.

Objectives

In this single-center retrospective study, the relationship between BCL-2 expression and blood venetoclax concentration was analyzed in 35 patients with AML. After that, we explored the differences in curative effect, adverse reactions, and outcomes between patients with different BCL-2 expression levels and patients with different venetoclax concentration levels, respectively.

Methods

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.

Results

The results revealed that among patients with AML, those with lower primary BCL-2 expression had a higher complete remission (CR) rate ( =0.005), overall response (OR) rate ( <0.0001), and progression-free survival time ( =0.04). Posaconazole was revealed to be a strong factor that was able to increase blood venetoclax concentration ( <0.001) and CR rate in the venetoclax plus posaconazole group compared to that in the venetoclax monotherapy group ( =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 ( =0.013).

Conclusion

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 (EFS).

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2025-01-08
2025-11-07

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/content/journals/pra/10.2174/0115748928330206241104161111
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Effect of Oral Posaconazole on Venetoclax Plasma Concentration and its Efficacy in Patients with Acute Myeloid Leukemia
Bentham Science Publishers ; https://doi.org/10.2174/0115748928330206241104161111
/content/journals/pra/10.2174/0115748928330206241104161111
/content/journals/pra/10.2174/0115748928330206241104161111
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  • Article Type:     Research Article
Keywords: BCL-2 inhibitor ; BCL-2 expression ; venetoclax ; posaconazole ; Acute myeloid leukemia

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