Early G-CSF after venetoclax-based induction for acute myeloid leukemia: Multicenter associations with infections, neutrophil recovery, and early mortality.

6518 Background: Venetoclax-based induction has improved remission rates in acute myeloid leukemia (AML) but is associated with prolonged neutropenia and infectious mortality. Optimal G-CSF timing remains uncertain. Methods: Multicenter real-world cohort (2018–2025) using TriNetX data across 21 U.S. institutions. Adults with newly diagnosed AML treated with venetoclax + hypomethylating agent or low-dose cytarabine were included. Early G-CSF was defined as initiation ≤ day 7 of cycle 1; deferred/none = > day 7 or none. The primary endpoint was grade ≥ 3 infection through day 42 (death as a competing risk, Fine–Gray models). Secondary endpoints: febrile neutropenia (FN), time to ANC ≥ 1.0 × 10⁹/L, ICU admission ≤ day 42, 60-day mortality, CR/CRi by day 60, and overall survival (OS). Multivariable models adjusted for age, ECOG, ELN risk, cytogenetics, baseline ANC/WBC, TP53/IDH/NPM1 mutations, antibacterial prophylaxis, and center effects. Results: N = 2,934; median age = 69 y (range 34–87). Early G-CSF = 39 %, deferred/none = 61 %. Early G-CSF lowered grade ≥ 3 infections (sHR 0.61 95 % CI 0.49–0.76, p < 0.001) and shortened ANC recovery (Δ –3.2 days –4.6 to –1.9, p < 0.001). FN risk was similar (aOR 0.94 0.79–1.12, p = 0.49). CR/CRi by day 60 (aOR 1.06 0.90–1.25, p = 0.47), OS (aHR 0.97 0.85–1.11, p = 0.65), and 60-day mortality (aOR 0.92 0.73–1.16, p = 0.49) were comparable. Findings persisted in age ≥ 75 and ELN-adverse subsets and remained robust after inverse-probability weighting and landmark analyses. Conclusions: Early (≤ day 7) G-CSF after venetoclax-based AML induction reduced severe infections and accelerated neutrophil recovery without affecting remission or survival. Results support standardized early G-CSF use to improve supportive-care safety, especially for older or high-risk patients. Early G-CSF timing and clinical outcomes after venetoclax-based AML induction. Outcome Deferred/None Early G-CSF Adjusted effect (95 % CI) P value Grade ≥3 infection ≤ day 42, % 31.4 21.2 sHR 0.61 (0.49–0.76) <0.001 Time to ANC ≥1.0 (days, median) 11.8 8.6 Δ –3.2 (–4.6 to –1.9) <0.001 Febrile neutropenia, % 38.9 37.4 aOR 0.94 (0.79–1.12) 0.49 ICU admission ≤ day 42, % 14.6 11.9 aOR 0.80 (0.65–0.99) 0.04 60-day mortality, % 10.1 9.3 aOR 0.92 (0.73–1.16) 0.49 CR/CRi by day 60, % 63.8 64.9 aOR 1.06 (0.90–1.25) 0.47 Abbreviations: sHR = sub-hazard ratio; aOR = adjusted odds ratio; aHR = adjusted hazard ratio; Δ = difference in medians. All models adjusted for baseline covariates (age, ELN risk, ECOG, cytogenetics, molecular subtype, prophylaxis use) and center effects.