Isavuconazole as Primary Antifungal Prophylaxis in Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome: An Open-label, Prospective, Phase 2 Study.

Autor:	Bose P; Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, Texas, USA., McCue D; Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Wurster S; Department of Infectious Diseases, University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Wiederhold NP; Fungus Testing Laboratory, Department of Pathology and Laboratory Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA., Konopleva M; Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Kadia TM; Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Borthakur G; Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Ravandi F; Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Masarova L; Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Takahashi K; Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Estrov Z; Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Yilmaz M; Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Daver N; Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Pemmaraju N; Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Naqvi K; Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Rausch CR; Division of Pharmacy, University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Marx KR; Division of Pharmacy, University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Qiao W; Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Huang X; Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Bivins CA; Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Pierce SA; Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Kantarjian HM; Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Kontoyiannis DP; Department of Infectious Diseases, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Jazyk:	angličtina
Zdroj:	Clinical infectious diseases : an official publication of the Infectious Diseases Society of America [Clin Infect Dis] 2021 May 18; Vol. 72 (10), pp. 1755-1763.
DOI:	10.1093/cid/ciaa358
Abstrakt:	Background: Mold-active primary antifungal prophylaxis (PAP) is routinely recommended in neutropenic patients with newly diagnosed acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS) undergoing remission-induction chemotherapy (RIC). Isavuconazole (ISAV) is an extended spectrum mold-active triazole and has superior tolerability and fewer significant drug-drug interactions compared with other triazoles. Methods: In our investigator-initiated, phase 2 trial, treatment-naive adult patients with AML or MDS starting RIC received ISAV per the dosing recommendations in the US label until neutrophil recovery (absolute neutrophil count [ANC] ≥ 0.5 × 109/L) and attainment of complete remission, occurrence of invasive fungal infection (IFI), or for a maximum of 12 weeks. The primary endpoint was the incidence of proven/probable IFI during ISAV PAP and up to 30 days after the last dose. Results: Sixty-five of 75 enrolled patients received ISAV PAP (median age, 67 years, median ANC at enrollment, 0.72 × 109/L). Thirty-two patients (49%) received oral targeted leukemia treatments (venetoclax, FTL3 inhibitors). Including the 30-day follow-up period, probable/proven and possible IFIs were encountered in 4 (6%) and 8 patients (12%), respectively. ISAV trough serum concentrations were consistently > 1 µg/mL, showed low intraindividual variation, and were not significantly influenced by chemotherapy regimen. Tolerability of ISAV was excellent, with only 3 cases (5%) of mild to moderate elevations of liver function tests and no QTc prolongations. Conclusions: ISAV is a safe and effective alternative for PAP in patients with newly diagnosed AML/MDS undergoing RIC in the era of recently approved or emerging small-molecule antileukemia therapies. Clinical Trials Registration: NCT03019939. (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu