Duration of cytopenias with concomitant venetoclax and azole antifungals in acute myeloid leukemia.
Duration of cytopenias with concomitant venetoclax and azole antifungals in acute myeloid leukemia.
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DOI：
10.1002/cncr.33508
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发表时间：
2021-07-15
期刊：
影响因子：
6.2
通讯作者：
Konopleva MY
中科院分区：
文献类型：
--
作者：
Rausch CR;DiNardo CD;Maiti A;Jammal NJ;Kadia TM;Marx KR;Borthakur G;Savoy JM;Pemmaraju N;DiPippo AJ;Daver NG;Chew SM;Sasaki K;Issa GC;Short NJ;Takahashi K;Ohanian MN;Ning J;Xiao L;Alvarado Y;Kontoyiannis DP;Ravandi F;Kantarjian HM;Konopleva MY
万乃馨联合去甲基化药物阿扎替丁可提高75岁≥初诊急性髓系白血病患者的存活率。使用VEN-HMA治疗可导致长期且通常是严重的中性粒细胞减少，因此需要进行抗真菌预防。唑类抗真菌药抑制负责VEN新陈代谢的主要酶--细胞色素P3A4，导致VEN剂量减少。关于接受VEN-HMA和各种唑类药物治疗的患者的结果，临床数据有限。对1个疗程后缓解的初诊AML患者的中性粒细胞恢复时间(ANC>；1000个/mm~3)和血小板恢复时间(PLT>；100,000个/mm~3)进行了评估。阿扎替丁75 mg/m2，静脉滴注，疗程7天；地西他滨20 mg/m2，静脉滴注，疗程5~10天。47例患者(73%)接受了唑类药物治疗，包括泊沙康唑(n=17；27%)、伏立康唑(n=9；14%)、异乌康唑(n=20；31%)或氟康唑(n=1；2%)。接受(37天；95%可信区间：34，38)或未接受(39天；95%可信区间：30，NA)的患者ANC恢复的中位时间相似(p=0.8)。接受唑类药物治疗的患者PLT恢复的中位时间明显较长(28天比22天，p=0.01)。泊沙康唑和伏立康唑的ANC和PLT恢复的中位时间(分别为35天和38天)和(26天和32天)相似。Ven-HMA导致中性粒细胞减少和血小板减少，后者在接受联合唑类药物治疗的患者中延长。联合应用泊沙康唑或伏立康唑与VEN 100 mg的ANC和PLT恢复时间相似，提示这些剂量组合在疗程1期间是安全的。在VEN和HMA治疗期间预防使用唑类抗真菌药物会影响血小板减少的持续时间，但不影响中性粒细胞减少的持续时间。VEN每日100毫克与泊沙康唑或伏立康唑联合使用可导致类似持续时间的细胞减少。
Venetoclax (VEN) combined with the hypomethylating agent (HMA) azacitidine improves survival in patients ≥75 years of age with newly diagnosed acute myeloid leukemia (AML). Treatment with VEN-HMA can result in prolonged and often profound neutropenia, warranting antifungal prophylaxis. Azole antifungals inhibit CYP3A4, the primary enzyme responsible for VEN metabolism, resulting in VEN dose reductions for each concomitant antifungal. Limited clinical data exists on outcomes in patients treated with VEN-HMA and various azoles. Time to neutrophil recovery (ANC>1000 cells/mm3) and platelet recovery (PLT>100,000 cells/mm3) in 64 patients with newly diagnosed AML who achieved a response after course 1 VEN-HMA was evaluated. HMA therapy included azacitidine 75 mg/m2 IV/SC for 7 days or decitabine 20 mg/m2 IV for 5 or 10 days. Forty-seven patients (73%) received an azole, including posaconazole (n=17; 27%), voriconazole (n=9; 14%), isavuconazole (n=20; 31%), or fluconazole (n=1; 2%). Median time to ANC recovery was similar between patients who did (37 days; 95%CI: 34, 38) or did not (39 days; 95%CI: 30, NA) receive an azole (p=0.8). Median time to PLT recovery was significantly longer in patients receiving azoles (28 vs 22 days, p=0.01). Median time to ANC (35 vs 38 days) and PLT (26 vs 32 days) recovery was similar between posaconazole and voriconazole. VEN-HMA results in neutropenia and thrombocytopenia, with the latter prolonged in patients receiving concomitant azoles. Concomitant posaconazole or voriconazole and VEN 100mg resulted in similar ANC and PLT recovery time, suggesting the safety of these dosage combinations during course 1. Prophylaxis with azole antifungal agents during VEN and HMA therapy impacted duration of thrombocytopenia but not neutropenia. The combination of VEN 100 mg daily and either posaconazole or voriconazole resulted in similar durations of cytopenias.
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DOI：
10.1016/s2352-3026(20)30210-6
发表时间：
2020-10
期刊：
The Lancet. Haematology
影响因子：
--
作者：
DiNardo CD;Maiti A;Rausch CR;Pemmaraju N;Naqvi K;Daver NG;Kadia TM;Borthakur G;Ohanian M;Alvarado Y;Issa GC;Montalban-Bravo G;Short NJ;Yilmaz M;Bose P;Jabbour EJ;Takahashi K;Burger JA;Garcia-Manero G;Jain N;Kornblau SM;Thompson PA;Estrov Z;Masarova L;Sasaki K;Verstovsek S;Ferrajoli A;Weirda WG;Wang SA;Konoplev S;Chen Z;Pierce SA;Ning J;Qiao W;Ravandi F;Andreeff M;Welch JS;Kantarjian HM;Konopleva MY
通讯作者：
Konopleva MY
影响因子：
11.8
作者：
BOW, EJ;LOEWEN, R;SCHACTER, B
通讯作者：
SCHACTER, B
影响因子：
3.2
作者：
Agarwal, Suresh K.;DiNardo, Courtney D.;Salem, Ahmed Hamed
通讯作者：
Salem, Ahmed Hamed
影响因子：
24.7
作者：
Short, Nicholas J.;Kantarjian, Hagop M.;Ravandi, Farhad
通讯作者：
Ravandi, Farhad
影响因子：
7.5
作者：
Aldoss, Ibrahim;Dadwal, Sanjeet;Pullarkat, Vinod
通讯作者：
Pullarkat, Vinod