Pretransplantation Hypomethylating Agents and Venetoclax in Acute Myeloid Leukemia Patients: A Real-World Analysis from the Cooperative Transplant Study Group
Year: 2025
Type: article
Study design: Observational Study
Abstract: The combination of hypomethylating agents (HMA) and the BCL2 inhibitor venetoclax (VEN) has become standard first-line therapy for acute myeloid leukemia (AML) patients ineligible for intensive treatment and also is used as salvage therapy in relapsed/refractory (R/R) AML. Data on outcomes after subsequent allogeneic stem cell transplantation (allo-SCT) are limited. We retrospectively analyzed 91 patients with newly diagnosed (ND; n = 34) or R/R (n = 57) AML who received HMA/VEN followed by allo-SCT between 2020 and 2022. The overall response rate to HMA/VEN was 67%, with no significant difference between ND patients (73%) and R/R patients (64%). Pretransplantation measurable residual disease negativity was achieved in 49% of responders. Post-transplantation 2-year overall survival (OS) and relapse-free survival (RFS) were 52% and 42%, respectively, for the entire cohort, with similar outcomes for ND (2-year OS, 47%; RFS, 38%) and R/R (2-year OS, 56%; RFS, 45%) patients. In patients with high-risk features, such as TP53 mutation or complex karyotype (cKT), ND patients still achieved promising responses (TP53mut, 75%; cKT, 80%) and acceptable post-transplantation outcomes (2-year OS: TP53mut, 36%; cKT, 45%). In contrast, R/R patients showed lower response rates (TP53mut, 14%; cKT, 29%) and inferior outcomes (2-year OS: TP53mut, 29%; cKT, 29%). In conclusion, HMA/VEN is a feasible induction or salvage strategy enabling allo-SCT with encouraging outcomes in high-risk populations. In ND AML, this approach may expand transplant eligibility in older and frail patients; R/R patients with adverse molecular features may require alternative novel therapies or direct transplantation.
Authors: Christina Rautenberg, Matthias Stelljes, Gesine Bug, Udo Holtick, Edgar Jost, Sara Jennrich, Annemarie Mohring, Johanna Tischer, Alessia Fraccaroli, Christoph Schliemann, Laura K. Schmalbrock, Lars Bullinger, Judith Metzdorf, Krischan Braitsch, Mareike Verbeek, Katharina Götze, Fabian Acker, H. Christian Reinhardt, Nicolaus Kröger, Thomas Schroeder
Institutions: Essen University Hospital, University Hospital Münster, University Hospital Frankfurt, University of Cologne, University Hospital Cologne, Universitätsklinikum Aachen, RWTH Aachen University, Ludwig-Maximilians-Universität München, German Cancer Research Center, Charité - Universitätsmedizin Berlin, TUM Klinikum, Technical University of Munich, University Medical Center Hamburg-Eppendorf
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,650
OpenAlex ID: W4417332441