Treatment outcomes and safety of reduced‑dose venetoclax plus antifungal agents to treat acute myeloid leukemia: A single hospital experience in Taiwan.

Abstract

Venetoclax, an orally administered B-cell lymphoma 2 inhibitor, requires dose adjustments when coadministered with cytochrome P450 inhibitors in patients with acute myeloid leukemia (AML). The present study retrospectively analyzed data on progression-free survival (PFS), overall survival (OS) and drug-related adverse events in patients with AML who received adjusted low-dose venetoclax with antifungal agents, compared with those receiving conventional chemotherapy regimens (I3A7, LDAC, and I2A5), at a single hospital. In total, 45 patients with AML who were treated between January 2015 and December 2021 were retrospectively included. A significantly longer median OS time was observed in the group receiving idarubicin [12 mg/m² intravenous (IV) on days 1-3] and cytarabine (100 mg/m² continuous IV infusion on days 1-7) (I3A7 group) (median not reached) compared with that in the venetoclax group [10.7 months; 95% confidence interval (CI), 6.3-20.8], the low-dose cytarabine (LDAC) group (4.7 months; 95% CI, 0.8-18.7) and the group receiving idarubicin (12 mg/m² IV on days 1-2) with cytarabine (100 mg/m² continuous IV infusion on days 1-5) (I2A5 group) (2.3 months; 95% CI, 0.5-2.3). Similarly, the median PFS time was significantly longer in the I3A7 group (29.0 months; 95% CI, 1.1-29.0) compared with that in the venetoclax (8.0 months; 95% CI, 0.8-10.8), LDAC (2.1 months; 95% CI, 0.1-6.4) and I2A5 (0.9 months; 95% CI, 0.1-4.7) groups. Grade 3 or higher adverse hematological events were common across all treatment groups. Cardiovascular events and grade 3 or higher tumor lysis syndrome occurred only in the venetoclax group (14 and 7%, respectively). In conclusion, low-dose venetoclax combined with antifungal agents appears to be less effective than standard treatment but superior to both LDAC and the I2A5 treatment regimens. Venetoclax also demonstrates a relatively low infection risk. However, careful monitoring for cardiovascular events and tumor lysis syndrome during venetoclax administration is crucial, particularly in patients with relevant medical histories.