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

Prithviraj Bose, David McCue, Sebastian Wurster, Nathan P. Wiederhold, Marina Konopleva, Tapan M. Kadia, Gautam Borthakur, Farhad Ravandi, Lucia Masarova, Koichi Takahashi, Zeev Estrov, Musa Yilmaz, Naval Daver, Naveen Pemmaraju, Kiran Naqvi, Caitlin R. Rausch, Kayleigh R. Marx, Wei Qiao, Xuelin Huang, Carol A. BivinsSherry A. Pierce, Hagop M. Kantarjian, Dimitrios P. Kontoyiannis

Research output: Contribution to journalArticlepeer-review

50 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1755-1763
Number of pages9
JournalClinical Infectious Diseases
Issue number10
StatePublished - May 15 2021


  • Antifungal prophylaxis
  • Chemotherapy
  • Invasive fungal infection
  • Isavuconazole
  • Leukemia

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases


Dive into the research topics of 'Isavuconazole as Primary Antifungal Prophylaxis in Patients with Acute Myeloid Leukemia or Myelodysplastic Syndrome: An Open-label, Prospective, Phase 2 Study'. Together they form a unique fingerprint.

Cite this