Venetoclax/azacitidine vs intensive chemotherapy as a bridge to allogeneic HSCT in AML: Experience from Ukraine.

Abstract

e18539 Background: Allogeneic stem cell transplantation (alloSCT) is the curative standard for high- and intermediate-risk acute myeloid leukemia (AML). However, refractory disease, age, comorbidities, and resource constraints impact transplantation eligibility. Venetoclax-azacitidine (VEN-AZA) offers a lower-toxicity bridging alternative to intensive chemotherapy (IC). In low-to-middle-income countries (LMICs) like Ukraine, where healthcare resources are limited and military conflict persists, safe and effective treatment options are critically needed. Methods: This single-center retrospective study evaluated VEN-AZA as a bridging therapy to alloSCT in AML. A total of 32 adult patients (median age: 33 years, range 18–64) were treated at the National Children’s Hospital “Ohmatdyt,” Kyiv, Ukraine (2022–2024). VEN-AZA Group (n=15, 47%) received up to two cycles due to poor performance status (12/15) or refractory disease (9/15). Ineligibility for IC was determined by ECOG score (≥2) with individualized consideration of comorbidities. IC Group (n=17, 53%) received cytarabine/idarubicin-based IC (7+3 or Ida-FLA). All patients proceeded to alloSCT: 30 after complete remission and 2 after partial response. Results: The VEN-AZA group had a 1-year OS of 68.4% (95% CI: 25.2–90.1) and EFS of 60.8% (95% CI: 22.8–84.6), while the IC group had a 1-year OS of 73.9% (95% CI: 44.2–89.4) and EFS of 68.2% (95% CI: 39.5–85.4). Cumulative relapse rates were 20% (3/15) for VEN-AZA and 23% (4/17) for IC. Early transplant-related mortality (≤180 days) was 6.6% (1/15) for VEN-AZA and 11% (2/17) for IC. Median follow-up was 317 days (VEN-AZA) and 566 days (IC). Conclusions: VEN-AZA provides an effective, low-toxicity alternative for bridging high-risk AML patients to alloSCT, achieving comparable survival to IC while expanding transplant eligibility. This regimen has the potential to refine treatment strategies, particularly in resource-limited settings. Prospective studies are warranted to validate these findings. Patient demographics and characteristics. Total patients(n=32) AZA-VEN Group (n=15) IC Group (n=17) Patients characteristics  Median age (years) 33 (18-64) 37 30  Sex, M (%) 14 (43%) 6 (40%) 8 (47%)  Unfit for IC 15 12 0  Fit for IC 20 3 17  Refractory disease* 17 9 8  > ICR 3 3 0  > 1st alloSCT 2 2 0 Risk category at diagnosis (ELN 2022 risk classification)  Unfavorable 24 10 14  Intermediate 8 5 3 Conditioning regimen  RIC 29 13 16  MAC 3 2 1 Donor type  Haplo 17 10 7  MUD 11 5 6  MRD 3 1 2 Median follow-up (days) 317 241 566 *Required switch to AZA-VEN or intensification of CT and/or positive minimal residual disease by flow cytometry. MRD – Matched related donor, MUD – Matched unrelated, Haplo – haploidentical, RIC – Reduced-intensity conditioning, MAC – Myeloablative conditioning.