Isavuconazole an attractive antifungal prophylactic in acute myeloid leukaemia/myelodysplastic syndrome
Isavuconazole (ISAV), an extended spectrum mold-active triazole, is safe and effective as primary antifungal prophylaxis (PAP) in patients with acute myeloid leukaemia (AML) or high-risk myelodysplastic syndrome (MDS) undergoing remission-induction chemotherapy, according to the results of a phase II study.
The trial enrolled 75 patients, of whom 65 (median age, 67 years; median absolute neutrophil count [ANC], 0.72 x 109/L) received ISAV PAP per the dosing recommendations in the label until neutrophil recovery (ANC ≥0.5 x 109/L) and attainment of complete remission, occurrence of invasive fungal infection (IFI), or for a maximum of 12 weeks.
About half of the population (n=32) received oral targeted leukaemia treatments (venetoclax, FTL3 inhibitors). The primary endpoint of proven/probable IFI during ISAV PAP and up to 30 days after the last dose occurred in 10 patients (15 percent). All patients were profoundly neutropaenic (ANC, 0.00–0.13) and not in complete remission when they developed IFI.
IFI occurred a median of 22 days from initiation of ISAV prophylaxis. All 10 patients with IFIs received antifungal treatment (liposomal amphotericin B with another triazole in seven, caspofungin plus posaconazole in two, posaconazole alone in one).
ISAV trough serum concentrations on days 8 and 15 were >1 µg/mL, with low intra-individual variation and not significantly altered by the patients’ chemotherapy regimen.
The drug was well tolerated, with only two cases of grade 1 transaminitis and another case of elevated total bilirubin. None of the patients had QTc prolongation while on ISAV, with median QTc times at baseline and on day 10 being 404 and 402 ms, respectively.