TY - JOUR
T1 - Isavuconazole as Primary Antifungal Prophylaxis in Patients with Acute Myeloid Leukemia or Myelodysplastic Syndrome
T2 - An Open-label, Prospective, Phase 2 Study
AU - Bose, Prithviraj
AU - McCue, David
AU - Wurster, Sebastian
AU - Wiederhold, Nathan P.
AU - Konopleva, Marina
AU - Kadia, Tapan M.
AU - Borthakur, Gautam
AU - Ravandi, Farhad
AU - Masarova, Lucia
AU - Takahashi, Koichi
AU - Estrov, Zeev
AU - Yilmaz, Musa
AU - Daver, Naval
AU - Pemmaraju, Naveen
AU - Naqvi, Kiran
AU - Rausch, Caitlin R.
AU - Marx, Kayleigh R.
AU - Qiao, Wei
AU - Huang, Xuelin
AU - Bivins, Carol A.
AU - Pierce, Sherry A.
AU - Kantarjian, Hagop M.
AU - Kontoyiannis, Dimitrios P.
N1 - Publisher Copyright:
© 2020
PY - 2021/5/15
Y1 - 2021/5/15
N2 - 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.
AB - 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.
KW - Antifungal prophylaxis
KW - Chemotherapy
KW - Invasive fungal infection
KW - Isavuconazole
KW - Leukemia
UR - http://www.scopus.com/inward/record.url?scp=85092169897&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85092169897&partnerID=8YFLogxK
U2 - 10.1093/cid/ciaa358
DO - 10.1093/cid/ciaa358
M3 - Article
C2 - 32236406
AN - SCOPUS:85092169897
SN - 1058-4838
VL - 72
SP - 1755
EP - 1763
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 10
ER -