Azole antifungals safe, effective in patients on midostaurin for FLT3 AML

The use of azole antifungal medications concurrently or sequentially with midostaurin is both safe and effective for patients with newly diagnosed FMS-like tyrosine kinase 3 mutated (FLT3m) acute myeloid leukaemia (AML), reports a study.

Forty patients were retrospective reviewed from 2017 to 2022 in this study. The authors then compared the efficacy and safety outcomes in patients treated with azole antifungals concurrently with those who did not receive an azole or received it sequentially to midostaurin for the treatment of FLT3m AML.

Both cohorts had a median age of about 55 years, and 70 percent of participants had FLT3 internal tandem duplication mutations. Patients in the concurrent arm received either posaconazole (33 percent) or isavuconazole (50 percent) for antifungal prophylaxis and micafungin (72 percent) for the sequential/no azole arm.

The overall complete remission or complete remission with incomplete hematologic recovery rates were similar between the concurrent and sequential/no azole arms (72 percent and 77 percent). The rates of nonhematologic grade 3 toxicities were 22 percent and 40 percent, respectively (p=0.21).

No between-group difference was also noted in the rates of dose reductions (6 percent vs 0 percent; p=0.26) and held doses (17 percent vs 14 percent; p=0.79). Likewise, there were no difference seen in new fungal infection rates during induction between the two groups.

“Additional confirmatory studies are needed due to our limited sample size,” the authors said. 

“Midostaurin is a multikinase inhibitor approved for the treatment of adult patients with newly diagnosed FLT3m AML. Azole antifungal medications are commonly used in AML and are known to interact with anticancer drugs such as midostaurin through the CYP3A pathway,” they added.