The Impact of Induction With Azacitidine and Venetoclax Versus Intensive Chemotherapy on Outcomes After Allogeneic Hematopoietic Cell Transplantation for Newly Diagnosed Acute Myeloid Leukemia

Abstract

Background: Induction with azacitidine and venetoclax (AZA-VEN) is standard therapy for patients 75 years or older or those with comorbidities that preclude intensive chemotherapy (IC) for acute myeloid leukemia (AML). Data on the impact of AZA-VEN on allogeneic hematopoietic cell transplant (HCT) outcomes in younger, fit patients are limited.

Methods: In a single-center retrospective study, we examined adult patients with newly diagnosed AML receiving either AZA-VEN or IC (cytarabine and anthracycline) to attain first complete remission (CR) before allogeneic HCT with posttransplant cyclophosphamide-based graft-versus-host disease (GVHD) prophylaxis between 2023 and 2025.

Results: The median age in the AZA-VEN (N = 14) and IC (N = 17) groups was similar (67 years (62–69) vs. 63 years (54–66), P = 0.13). The AZA-VEN group had more adverse-risk AML (93% vs. 41%, P = 0.001). Otherwise, there were no significant differences in Hematopoietic Cell Transplantation Comorbidity Index, secondary AML incidence, minimal residual disease (MRD) status, or donor types between the two cohorts. The AZA-VEN and IC cohorts had similar 1-year overall survival (69.2%, 95% confidence interval (CI) (48.2–99.5) vs. 75%, 95% CI (56.5–99.7), P = 0.73), 1-year relapse-free survival (57.1%, 95% CI (36.3–89.9) vs. 64.7%, 95% CI (45.5–91.9), P = 0.67), 1-year GVHD-free relapse-free survival (57.1%, 95% CI (36.3–89.9) vs. 64.7% 95% CI (45.5–91.9), P = 0.67), 1-year cumulative incidence of relapse (14.3% vs. 11.8%, P = 0.84), 1-year cumulative incidence of non-relapse mortality (28.5% vs. 23.5%, P = 0.76), 1-year cumulative incidence of grade 3–4 acute GVHD (14.3% vs. 5.9%, P = 0.46), and 1-year cumulative incidence of chronic GVHD (7.1% vs. 11.8 %, P = 0.67). On multivariable Cox analysis, there was no significant impact of treatment cohort (AZA-VEN vs. IC), MRD, adverse-risk genetics, acute GVHD, Hematopoietic Cell Transplantation Comorbidity Index, or age on overall survival.