Venetoclax combined with high-dose cytarabine and mitoxantrone for relapsed or refractory acute myeloid leukemia: outcomes and risk stratification

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.

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Journal
Haematologica
Published
2026-08-20
DOI
https://doi.org/10.3324/haematol.2026.301102
Primary Topic
Acute Myeloid Leukemia Research
Type
article
Field-Weighted Citation Impact
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article

Venetoclax combined with high-dose cytarabine and mitoxantrone for relapsed or refractory acute myeloid leukemia: outcomes and risk stratification

Clara Burkhard-Meier, Kai Wille, Krischan Braitsch, Andrew F. Berdel et al.
Haematologica
Acute Myeloid Leukemia Research
article

Venetoclax combined with high-dose cytarabine and mitoxantrone for relapsed or refractory acute myeloid leukemia: outcomes and risk stratification

Clara Burkhard-Meier, Kai Wille, Krischan Braitsch, Andrew F. Berdel, Paul Jaeger, Jan Moritz Middeke, Christoph Kiefel, Edgar Jost, Klaus Wethmar, Leo Ruhnke, Christoph Schliemann, Maher Hanoun, Marcel Kemper, Tim Sauer, Marco Tembrink, Katharina Götze, Sylvia Herold, Claudia Baldus, Julia M. Unglaub, Klaus Metzeler, Hubert Serve, Martina Crysandt, Björn Steffen, Nardos Hölscher, Jan-Henrik Mikesch, Martin Bornhäuser, Georg Lenz, Carsten Müller-Tidow, Andreas Burchert, Andreas Rank, Christian Thiede, Sara Hilber, Christoph Röllig, Kerstin Schäfer-Eckart, Johannes Schetelig, Martin Kaufmann, Mathias Hänel, Thomas Schroeder, Matthias Stelljes, Lukas Frenzel, David Poitz, Uwe Platzbecker, Julian Ronnacker, Lars Fransecky
article en

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.

Haematologica
Goethe University Frankfurt (DE), Philipps University of Marburg (DE), Heidelberg University (DE), University Hospital Augsburg (DE), University Hospital Heidelberg (DE), Robert Bosch Hospital (DE), Düsseldorf University Hospital (DE), Integrated Oncology (United States) (US), Nuremberg Hospital (DE), University Hospital Münster (DE), University Hospital Schleswig-Holstein (DE), Klinikum Braunschweig (DE), Essen University Hospital (DE), München Klinik (DE), University Hospital Leipzig (DE), University Hospital Frankfurt (DE), Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (DE), University Hospital Cologne (DE), Klinikum Chemnitz (DE), Johannes Wesling Klinikum Minden (DE), Heinrich Heine University Düsseldorf (DE), University of Duisburg-Essen (DE), Technische Universität Dresden (DE), Leipzig University (DE), University of Lübeck (DE)
Pfizer, Deutsche Forschungsgemeinschaft, Westfälische Wilhelms-Universität Münster
Partnerships for the goals
Openalex Percentile: Top 10%
Acute Myeloid Leukemia Research
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