Venetoclax combined with high-dose cytarabine and mitoxantrone for relapsed or refractory acute myeloid leukemia: outcomes and risk stratification
Year: 2026
Type: article
Study design: Observational Study
Abstract: Relapsed or refractory acute myeloid leukemia (R/R AML) remains a therapeutic challenge, with standard high‑dose cytarabine-based salvage regimens achieving complete remission (CR) rates of around 50%. In the phase 1/2 RELAX trial, adding venetoclax (VEN) to high‑dose cytarabine and mitoxantrone (HAM) was considered safe and resulted in CR or CR with incomplete hematologic recovery (CRi) in 75% of patients. Here, we performed a multicenter real‑world analysis of 128 R/R AML patients treated with HAM plus VEN (VEN 400 mg days 1-14, cytarabine 1000 mg/m² IV twice daily days 3-5, mitoxantrone 10 mg/m² IV days 5-7) between March 2023 and June 2025. The median age was 60 years (range, 20-74). Patients had a median of 1 prior therapy (range, 1-5), 38% had prior allogeneic hematopoietic cell transplantation (HCT), and 25% VEN exposure. Overall, 69% achieved CR/CRi; response rates were higher in patients with one prior therapy line (78%) and VEN-naïve patients (76%). Sixty-eight percent proceeded to HCT. After a median follow-up of 11.5 months, estimated 1‑year RFS and OS rates were 59% and 58%, respectively. In a prognostic classifier derived from pooled real-world and RELAX trial data (183 patients), TP53 mutation, complex karyotype, ≥2 prior therapy lines, and Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2 predicted inferior outcomes. Patients without these features had a 1-year OS of 73%. HAM plus VEN retains high efficacy and encouraging survival outcomes in a real-world setting, supporting its use as an effective salvage and bridge-to-transplant strategy.
Source: Haematologica
Authors: Andrew F. Berdel, Christoph Röllig, Clara Burkhard-Meier, Marco Tembrink, Julia M. Unglaub, Tim Sauer, Martina Crysandt, Edgar Jost, Paul Jaeger, Christoph Kiefel, Lars Fransecky, Krischan Braitsch, Katharina Götze, Kai Wille, Kerstin Schäfer-Eckart, Klaus Metzeler, Sara Hilber, Julian Ronnacker, Marcel Kemper, Nardos Hölscher, Klaus Wethmar, Thomas Schroeder, Sylvia Herold, David Poitz, Björn Steffen, Andreas Rank, Mathias Hänel, Jan Moritz Middeke, Martin Kaufmann, Andreas Burchert, Johannes Schetelig, Uwe Platzbecker, Christian Thiede, Matthias Stelljes, Georg Lenz, Hubert Serve, Claudia Baldus, Martin Bornhäuser, Carsten Müller-Tidow, Jan-Henrik Mikesch, Lukas Frenzel, Maher Hanoun, Leo Ruhnke, Christoph Schliemann
Institutions: University Hospital Münster, Technische Universität Dresden, University of Cologne, University Hospital Cologne, Essen University Hospital, University of Duisburg-Essen, Heidelberg University, University Hospital Heidelberg, Universitätsklinikum Aachen, Heinrich Heine University Düsseldorf, University Hospital Schleswig-Holstein, TUM Klinikum, Technical University of Munich, Johannes Wesling Klinikum Minden, Paracelsus Medical University, Nuremberg Hospital, University Hospital Leipzig, Leipzig University, University Hospital Carl Gustav Carus, University Hospital Frankfurt, University Hospital Augsburg, Klinikum Chemnitz, Robert Bosch Hospital, Universitätsklinikum Gießen und Marburg, Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,157
OpenAlex ID: W7203821381
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