Duration of cytopenias with concomitant venetoclax and azole antifungals in acute myeloid leukemia
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- Caitlin R. Rausch
- Division of Pharmacy The University of Texas MD Anderson Cancer Center Houston Texas
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- Courtney D. DiNardo
- Department of Leukemia The University of Texas MD Anderson Cancer Center Houston Texas
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- Abhishek Maiti
- Department of Leukemia The University of Texas MD Anderson Cancer Center Houston Texas
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- Nadya J. Jammal
- Division of Pharmacy The University of Texas MD Anderson Cancer Center Houston Texas
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- Tapan M. Kadia
- Department of Leukemia The University of Texas MD Anderson Cancer Center Houston Texas
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- Kayleigh R. Marx
- Division of Pharmacy The University of Texas MD Anderson Cancer Center Houston Texas
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- Gautam Borthakur
- Department of Leukemia The University of Texas MD Anderson Cancer Center Houston Texas
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- J. Michael Savoy
- Division of Pharmacy The University of Texas MD Anderson Cancer Center Houston Texas
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- Naveen Pemmaraju
- Department of Leukemia The University of Texas MD Anderson Cancer Center Houston Texas
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- Adam J. DiPippo
- Division of Pharmacy The University of Texas MD Anderson Cancer Center Houston Texas
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- Naval G. Daver
- Department of Leukemia The University of Texas MD Anderson Cancer Center Houston Texas
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- Serena M. Chew
- Division of Pharmacy The University of Texas MD Anderson Cancer Center Houston Texas
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- Koji Sasaki
- Department of Leukemia The University of Texas MD Anderson Cancer Center Houston Texas
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- Ghayas C. Issa
- Department of Leukemia The University of Texas MD Anderson Cancer Center Houston Texas
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- Nicholas J. Short
- Department of Leukemia The University of Texas MD Anderson Cancer Center Houston Texas
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- Koichi Takahashi
- Department of Leukemia The University of Texas MD Anderson Cancer Center Houston Texas
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- Maro N. Ohanian
- Department of Leukemia The University of Texas MD Anderson Cancer Center Houston Texas
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- Jing Ning
- Department of Biostatistics The University of Texas MD Anderson Cancer Center Houston Texas
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- Lianchun Xiao
- Department of Biostatistics The University of Texas MD Anderson Cancer Center Houston Texas
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- Yesid Alvarado
- Department of Leukemia The University of Texas MD Anderson Cancer Center Houston Texas
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- Dimitrios P. Kontoyiannis
- Department of Infectious Diseases The University of Texas MD Anderson Cancer Center Houston Texas
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- Farhad Ravandi
- Department of Leukemia The University of Texas MD Anderson Cancer Center Houston Texas
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- Hagop M. Kantarjian
- Department of Leukemia The University of Texas MD Anderson Cancer Center Houston Texas
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- Marina Y. Konopleva
- Department of Leukemia The University of Texas MD Anderson Cancer Center Houston Texas
Description
<jats:sec><jats:title>Background</jats:title><jats:p>Venetoclax (VEN) combined with the hypomethylating agent (HMA) azacitidine improves survival in patients aged ≥75 years with newly diagnosed acute myeloid leukemia (AML). VEN and HMA treatment can result in prolonged and often profound neutropenia, and this warrants antifungal prophylaxis. Azole antifungals inhibit cytochrome P450 3A4, the primary enzyme responsible for VEN metabolism; this results in VEN dose reductions for each concomitant antifungal. Limited clinical data exist on outcomes for patients treated with VEN, an HMA, and various azoles.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>The time to neutrophil recovery (absolute neutrophil count [ANC] > 1000 cells/mm<jats:sup>3</jats:sup>) and platelet (PLT) recovery (PLT count > 100,000 cells/mm<jats:sup>3</jats:sup>) in 64 patients with newly diagnosed AML who achieved a response after course 1 of VEN plus an HMA were evaluated. HMA therapy included azacitidine (75 mg/m<jats:sup>2</jats:sup> intravenously/subcutaneously for 7 days) or decitabine (20 mg/m<jats:sup>2</jats:sup> intravenously for 5 or 10 days).</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Forty‐seven patients (73%) received an azole: posaconazole (n = 17; 27%), voriconazole (n = 9; 14%), isavuconazole (n = 20; 31%), or fluconazole (n = 1; 2%). The median time to ANC recovery were similar for patients who did receive an azole (37 days; 95% confidence interval [CI], 34‐38 days) and patients who did not receive an azole (39 days; 95% CI, 30 days to not estimable; <jats:italic>P</jats:italic> = .8). The median time to PLT recovery was significantly longer for patients receiving azoles (28 vs 22 days; <jats:italic>P</jats:italic> = .01). The median times to ANC recovery (35 vs 38 days) and PLT recovery (26 vs 32 days) were similar with posaconazole and voriconazole.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>VEN plus an HMA resulted in neutropenia and thrombocytopenia, with the latter prolonged in patients receiving concomitant azoles. Concomitant posaconazole or voriconazole and VEN (100 mg) resulted in similar ANC and PLT recovery times, suggesting the safety of these dosage combinations during course 1.</jats:p></jats:sec>
Journal
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- Cancer
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Cancer 127 (14), 2489-2499, 2021-04
Wiley
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Details 詳細情報について
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- CRID
- 1360580237013472896
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- ISSN
- 10970142
- 0008543X
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- Data Source
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- Crossref