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Duration of cytopenias with concomitant venetoclax and azole antifungals in acute myeloid leukemia

Rausch, Caitlin R. ; DiNardo, Courtney D. ; Maiti, Abhishek ; Jammal, Nadya J. ; Kadia, Tapan M. ; Marx, Kayleigh R. ; Borthakur, Gautam ; Savoy, J. Michael ; Pemmaraju, Naveen ; DiPippo, Adam J. ; Daver, Naval G. ; Chew, Serena M. ; Sasaki, Koji ; Issa, Ghayas C. ; Short, Nicholas J. ; Takahashi, Koichi ; Ohanian, Maro N. ; Ning, Jing ; Xiao, Lianchun ; Alvarado, Yesid ; Kontoyiannis, Dimitrios P. ; Ravandi, Farhad ; Kantarjian, Hagop M. ; Konopleva, Marina Y.

Cancer, 2021-07, Vol.127 (14), p.2489-2499 [Periódico revisado por pares]

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Título:
Duration of cytopenias with concomitant venetoclax and azole antifungals in acute myeloid leukemia
Autor: Rausch, Caitlin R. ; DiNardo, Courtney D. ; Maiti, Abhishek ; Jammal, Nadya J. ; Kadia, Tapan M. ; Marx, Kayleigh R. ; Borthakur, Gautam ; Savoy, J. Michael ; Pemmaraju, Naveen ; DiPippo, Adam J. ; Daver, Naval G. ; Chew, Serena M. ; Sasaki, Koji ; Issa, Ghayas C. ; Short, Nicholas J. ; Takahashi, Koichi ; Ohanian, Maro N. ; Ning, Jing ; Xiao, Lianchun ; Alvarado, Yesid ; Kontoyiannis, Dimitrios P. ; Ravandi, Farhad ; Kantarjian, Hagop M. ; Konopleva, Marina Y.
Assuntos: 5-aza-2'-deoxycytidine ; Acute myeloid leukemia ; Aged ; Antifungal Agents - adverse effects ; Antineoplastic Combined Chemotherapy Protocols - adverse effects ; azole antifungals ; Azoles ; Azoles - therapeutic use ; Bridged Bicyclo Compounds, Heterocyclic ; Confidence intervals ; Cytochrome ; Cytochrome P450 ; Cytochromes P450 ; Dosage ; Fluconazole ; Fungicides ; Heterocyclic compounds ; Humans ; invasive fungal infection ; Leukemia ; Leukemia, Myeloid, Acute ; Leukocytes (neutrophilic) ; Metabolism ; Myeloid leukemia ; Neutropenia ; Neutrophils ; Patients ; Posaconazole ; Prophylaxis ; Recovery ; Sulfonamides ; Thrombocytopenia ; Thrombocytopenia - chemically induced ; Thrombocytopenia - drug therapy ; venetoclax ; Voriconazole
É parte de: Cancer, 2021-07, Vol.127 (14), p.2489-2499
Notas: Authorship Contributions
CRR, CDD, AM, MK designed the study; CRR, CDD, AM, NJ, KRM, JMS, AD, SC, DPK, HK, MK collected and assembled data and contributed to manuscript preparation and editing; JN, LX performed statistical analyses; all authors analyzed and interpreted data and approved the final draft of the manuscript
Descrição: Background 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. Methods The time to neutrophil recovery (absolute neutrophil count [ANC] > 1000 cells/mm3) and platelet (PLT) recovery (PLT count > 100,000 cells/mm3) 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/m2 intravenously/subcutaneously for 7 days) or decitabine (20 mg/m2 intravenously for 5 or 10 days). Results 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; P = .8). The median time to PLT recovery was significantly longer for patients receiving azoles (28 vs 22 days; P = .01). The median times to ANC recovery (35 vs 38 days) and PLT recovery (26 vs 32 days) were similar with posaconazole and voriconazole. Conclusions 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. Prophylaxis with azole antifungal agents during venetoclax and hypomethylating agent therapy affects the duration of thrombocytopenia but not neutropenia. The combination of 100 mg daily of venetoclax and either posaconazole or voriconazole results in similar durations of cytopenias.
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Idioma: Inglês

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Duration of cytopenias with concomitant venetoclax and azole antifungals in acute myeloid leukemia

United States: Wiley Subscription Services, Inc

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