Infection Profiles Under Venetoclax-Based Therapy in Newly Diagnosed Acute Myeloid Leukemia: A Real-World Study.

Abstract

Venetoclax (VEN)-based regimens improve remission in acute myeloid leukemia (AML), but infectious toxicity remains a concern. We compared infection profiles under VEN-based versus conventional therapy in newly diagnosed, non-M3 AML at a single tertiary center (2015-2024; n = 358; VEN = 156; non-VEN = 202). After 1:1 propensity-score matching on nine baseline covariates (115 per group), we assessed infection rates and event density (events per 1000 person-days) by site and pathogen, time to first infection (120-day cumulative incidence), and landmark associations between early infections and progression-free survival (PFS). Baseline predictors of microbiologically documented infection (MDI) were modeled in the pre-matching cohort. VEN was associated with higher febrile-neutropenia (FN) event density (IRR, 1.77; 95% CI, 1.33-2.36; p < 0.001; 16.40 vs. 9.27 per 1000 person-days). Site-level patterns diverged: upper-respiratory and lung infections showed lower first-event incidence with VEN, whereas skin/soft-tissue and perianal sites showed higher event density without higher patient-level incidence. By pathogen, bacterial and fungal first events were fewer with VEN while event densities were comparable; viral infections occurred earlier and accrued higher cumulative incidence. Cumulatively, the first infection was lower with VEN at days 30, 60, and 90 but converged by day 120. In the pre-matching cohort, higher HCT-CI (1-2/≥ 3 vs. 0) and higher DBIL independently predicted MDI, while female sex predicted lower risk. MDIs within 90 days-bacterial/fungal-driven-were associated with inferior PFS at 100 and 365 days, whereas early viral infections showed no association.