Allogeneic Hematopoietic Cell Transplantation in Newly Diagnosed and Relapse/Refractory AML Patients Post Venetoclax-Azacitidine Treatment: A Multicenter Real-Life Analysis By the French Auraml Group
Authors: Tauveron-Jalenques Urbain , Gross Zofia , Carre Martin , Tavernier Emmanuelle , Cornillon Jérôme , Contejean Adrien , Santana Clemence , Rocher Clément , Lamure Sylvain , Mauz Natacha , Thévenet Ugo , Nadine Boullanger Fow Heng , Gian-Matteo Pica , Arthur Dony , Belhabri Amine , Michallet Mauricette , Chorao Pedro , Heiblig Mael , Aspas Requena Gaspar 
Published: December 2024

Allogeneic hematopoietic stem cell transplantation (ASCT) remains the most effective curative treatment for patients with high-risk acute myeloid leukemia (AML). However, patients ineligible for intensive chemotherapy (IC) due to age or comorbidities have typically not been viable candidates. The therapeutic landscape of AML has recently evolved with the integration of the 5-azacitidine and venetoclax (AZA/VEN) combination regimen in newly diagnosed (ND) patients unfit for IC. Off-label use of AZA/VEN is also prevalent in the relapsed/refractory (R/R) setting. However, data regarding the safety and outcomes of ASCT in AZA/VEN-treated patients remain limited.
In this study, we aimed to evaluate the safety and efficacy of ASCT in AML patients treated with AZA/VEN in both ND and R/R settings.
We conducted a multicenter retrospective cohort study using data from the VENAURA registry, which includes 585 AML patients from 12 centers in the Auvergne Rhône Alpes (AURA) region of France treated with AZA/VEN between 2019 and 2024.
This study analyzed 80 AML patients who underwent ASCT after receiving AZA/VEN in either ND (25; 31%) or R/R (55; 69%) settings. The cohort included 40 patients (52%) with de novo AML, 13 (17%) with secondary AML, 10 (13%) with AML with Myelodysplasia-Related Changes (AML-MRC), and 14 (18%) with MDS/AML. The median age was 57 years (y) (range 18-73). Besides age (61 y vs. 56 y, p=0.048), there were no significant differences between the ND and R/R groups in other clinical characteristics, molecular features, or ELN 2022 risk groups.
No significant differences were observed between the groups for median number of AZA/VEN cycles before HSCT (2 cycles, range 1-6, p=1), median time from AZA/VEN initiation to ASCT (3 months, range 1-14, p=0.85), pre-ASCT response (complete remission (CR) in 61 patients, 76%; CR with incomplete hematologic recovery (CRi) in 7 patients, 9%; morphologic leukemia-free state (MLFS) in 7 patients, 9%; no response (NR) in 5 patients, 6%, p=0.75), or minimal residual disease (MRD) status (36 MRD-negative, 60%; 24 MRD-positive, 40%, p=0.58).
With a median follow-up period of 13 months (IQR 11-16), no significant differences were observed between ND and R/R groups regarding 1-year overall survival (72 vs 79%, p=0.34), non-relapse mortality at 1 year (4.3 vs 6.2%, p=0.86), or relapse rate at 1 year (21% vs 25%, p=0.91).
No significant differences were observed between groups regarding acute graft-versus-host disease (GVHD) (28% overall, 37% ND, 23% R/R, p=0.12), severe acute GVHD (9.6% overall, 8.1% ND, 10% R/R, p=0.98), or chronic GVHD incidence at 1 year (22% overall, 18% ND, 23% R/R, p=0.97).
In multivariate overall survival analysis, factors significantly associated with worse survival were age (HR 1.08 per y, 95% CI: 1.00-1.15, p=0.043), higher HCT-CI score (≥3) (HR 8.69, 95% CI: 2.27-33.3, p=0.002) and ELN 2022 adverse risk classification (HR 12.5, 95% CI: 1.52-103, p=0.019).
Concerning cumulative incidence of relapse, MRD positivity pre-ASCT remained significant (HR 4.53, 95% CI: 1.34-15.3, p=0.015), and donor type (matched vs mismatched) was nearly significant (HR 3.03, 95% CI: 0.99-9.35, p=0.053) in multivariate analysis.
In conclusion, our data suggest that ASCT for AZA/VEN treated AML patients is feasible, with promising transplant outcomes and an encouraging post-ASCT treatment-related mortality. Additionally, it is important to note that our results, collected in a real-world setting, involve older patients with inherently poor leukemia characteristics and a high number of mismatched donors. To establish the benefit of AZA/VEN pre-ASCT, a matching comparison with a CIBMTR historical control cohort treated with conventional IC will be presented during the meeting.