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3564 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

Program: Oral and Poster Abstracts
Session: 732. Allogeneic Transplantation: Disease Response and Comparative Treatment Studies: Poster II
Hematology Disease Topics & Pathways:
Research, Acute Myeloid Malignancies, AML, Combination therapy, Clinical Research, Diseases, Therapy sequence, Real-world evidence, Treatment Considerations, Registries, Myeloid Malignancies
Sunday, December 8, 2024, 6:00 PM-8:00 PM

Urbain Tauveron-Jalenques1*, Zofia Gross, MD2*, Martin Carre, MD3*, Emmanuelle Tavernier, MD4*, Jérôme Cornillon4*, Adrien Contejean5*, Clemence Santana6,7*, Clément Rocher, MD8*, Sylvain Lamure, MD, PhD9*, Natacha Mauz5*, Ugo Thévenet, MD10*, Boullanger Fow Heng Nadine11*, Pica Gian-Matteo12*, Dony Arthur, MD13*, Amine Belhabri, MD14*, Mauricette Michallet, MD, PhD14, Pedro Chorao, MD15*, Mael Heiblig16,17* and Gaspar Aspas Requena, MD1,18*

1Service d'Hématologie Clinique et Thérapie Cellulaire, CHU Clermont-Ferrand, Clermont-Ferrand, France
2Département d'Hématologie, CHU de Lyon, Pierre-Bénite, France
3Clinical Hematology Department, CHU Grenoble Alpes - Université Grenoble Alpes, Grenoble, France
4Département d'hématologie Clinique et de Thérapie Cellulaire, CHU Saint-Etienne, Saint-Etienne, France
5Département d'Hématologie, Centre Hospitalier Annecy Genevois, Epagny Metz-Tessy, France
6Centre Léon Bérard, LYON CEDEX 08, France
7CH Valence, Valence, FRA
8Département d'Hématologie, Centre Hospitalier Bourgoin Jallieu, Bourgoin Jallieu, France
9Département d'Onco-Hématologie, Hôpitaux Nord-Ouest, Villefranche-sur-Saone, France
10CH de Roanne, Roanne, France
11Département d'hématologe, CH Roanne, Roanne, France
12Service d’hématologie, CH Métropole Savoie, Chambéry, France
13Service d'hematologie, Hopital Chambery, Chambery, France
14Département de Cancérologie médicale, Centre Léon Bérard, Lyon, France
15Hematology Department, Hospital Universitari i Politècnic La Fe, Valencia, Spain
16Centre Hospitalier Lyon Sud, Centre Hospitalier Lyon Sud, Service Hématologie, Centre d’Investigation des thérapeutiques en oncologie et hématologie de Lyon (CITHOL), Vourles, Rhône Alpes, France
17Service d'hématologie clinique, Hospices Civils de Lyon, Hôpital Lyon Sud, Pierre-Bénite, France
18Université Clermont Auvergne, Clermont-Ferrand, France

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.

Disclosures: Tavernier: Pfizer: Other; BMS: Honoraria. Contejean: Novartis: Honoraria; Pfizer: Honoraria; Abbvie: Honoraria; BMS: Honoraria; Janssen: Honoraria. Santana: Abbvie: Other; BMS: Other; Astrazeneca: Other. Rocher: ASTRAZENECA: Consultancy; BRISTOL MYERS SQUIBB: Research Funding; Pierre OUDOT hospital: Current Employment. Lamure: Janssen: Other, Research Funding; Gilead: Other; Roche Pharma: Other; Abbvie: Other; Sanofi: Other; Novartis: Other; Actelion: Other; Pfizer: Other. Heiblig: Servier: Honoraria; Jazz pharmaceutical: Honoraria; Abbvie: Honoraria; Pfizer: Honoraria; Astellas: Honoraria. Aspas Requena: Janssen: Honoraria; BMS: Honoraria; Abbvie: Honoraria; NOVARTIS: Honoraria; Servier: Honoraria.

*signifies non-member of ASH