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693 Intensified Cytarabine Dose during Consolidation Therapy in AML Patients Under 65 Years Is Not Associated with Survival BenefitClinically Relevant Abstract

Program: Oral and Poster Abstracts
Type: Oral
Session: 615. Acute Myeloid Leukemias: Commercially Available Therapies, Excluding Transplantation and Cellular Immunotherapies: Current approach to FLT3 mutated AML
Hematology Disease Topics & Pathways:
Non-Biological, Clinical Research, Chemotherapy, Clinically Relevant, Therapies, Registries
Monday, December 13, 2021: 3:15 PM

Maher Hanoun, MD1*, Leo Ruhnke2*, Michael Kramer, MSc2*, Kerstin Schäfer-Eckhard, MD3*, Björn Steffen, MD4*, Tim Sauer, MD5*, Stefan W. Krause, MD6*, Christoph Schliemann, Prof., MD7*, Martin Kaufmann, MD8, Mathias Haenel9*, Edgar Jost10*, Tim H Brummendorf, MD11, Lars Fransecky, MD12*, Sabrina Kraus, MD13*, Hermann Einsele14, Dirk Niemann, MD15*, Andreas Neubauer16, Johannes Kullmer17*, Ruth Seggewiss-Bernhard18*, Martin Goerner, MD19*, Gerhard Held20*, Ulrich Kaiser, MD21*, Sebastian Scholl, MD, PhD22*, Hans Christian Reinhardt, MD1*, Uwe Platzbecker, MD23, Claudia D. Baldus, MD12*, Carsten Mueller-Tidow, MD5, Martin Bornhaeuser, MD24, Hubert Serve, MD4 and Christoph Rollig, MD, MSC25*

1Department of Hematology and Stem Cell Transplantation, University Hospital Essen, Essen, Germany
2Department of Internal Medicine I, University Hospital Dresden, Dresden, Germany
3Department of Internal Medicine 5, Hospital Nürnberg, Nürnberg, Germany
4Department of Medicine II, Hematology/Oncology, Goethe University, University Hospital, Frankfurt, Germany
5Department of Hematology, Oncology and Rheumatology, University Hospital Heidelberg, Heidelberg, Germany
6Department of Hematology and Medical Oncology, University Hospital Erlangen, Erlangen, Germany
7Department of Medicine A, Hematology, Oncology and Pneumology, University Hospital Muenster, Muenster, Germany
8Department of Hematology, Oncology and Palliative Medicine, Robert-Bosch-Hospital, Stuttgart, Germany
9Department of Internal Medicine III, Chemnitz Hospital, Chemnitz, Germany
10Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Medical Faculty, University Hospital Aachen, Aachen, Germany
11Department of Internal Medicine IV, University Hospital RWTH Aachen, Aachen, Germany
12Department of Internal Medicine II, University Hospital Schleswig-Holstein, Kiel, Germany
13Department of Medicine II, University Hospital of Wuerzburg, Wuerzburg, Germany
14Department of Internal Medicine II, University Hospital Würzburg, Würzburg, Germany
15Department of Hematology/Oncology and Palliative Medicine, Ev. Stift St. Martin, Koblenz, Germany
16Department of Hematology, Oncology and Immunology, University Hospital Marburg, Marburg, Germany
17Department of Internal Medicine II, DIAKO Bremen, Bremen, Germany
18Department of Internal Medicine V, Sozialstiftung Bamberg, Bamberg, Bavaria, Germany
19Department of Hematology, Oncology and Palliative Medicine, Klinikum Bielefeld Mitte, Bielefeld, Germany
20Department of Hematology, Oncology, Clinical Immunology, Rheumatology, University of Saarland, Homburg, Germany
21Department of Hematology and Oncology, St. Bernward Krankenhaus, Hildesheim, Germany
22University Hospital Jena, Jena, Germany
23Department for Internal Medicine I, University Hospital Leipzig, Leipzig, Germany
24Department of Internal Medicine I, University Hospital Carl Gustav Carus, Dresden, Germany
25Department of Internal Medicine I, University Hospital, Dresden, Germany

Background: Acute myeloid leukemia (AML) is characterized by a high relapse rate, indicating insufficient clearance of leukemia-initiating cells. Depending on genetic risk stratification, consolidating chemotherapy proves to significantly reduce the risk of relapse. In particular, in younger AML patients higher dosage of cytarabine appears to improve long-term outcome, while there is no apparent benefit of multiagent combination, compared to cytarabine monotherapy. However, to this end the optimal dosage of single agent cytarabine in consolidation therapy after 7+3 remission induction remains elusive.

Methods: Here, we retrospectively assessed the impact of different dosages of cytarabine consolidation on outcome in a large real-world data set from the German Study Alliance Leukemia-Acute Myeloid Leukemia (SAL-AML) registry. Patients below 65 years of age, registered between April 2005 and September 2020 with non-acute promyelocytic leukemia, who attained complete remission after intensive induction and received at least one consolidation cycle with intermediate (IDAC) or high dose cytarabine (HiDAC) were selected. To account for differences in patient and disease characteristics between both groups, the average treatment effect was estimated by propensity score weighting.

Results: 642 patients received HiDAC consolidation with a median dosage of 5794.88 (IQR, 4745.48-5971.56) mg/m2/d with a median number of 3 cycles (IQR, 2-3), whereas 178 patients received IDAC consolidation with 1946.16 (IQR, 1869.51-2469.15) mg/m2/d with a median of 2 cycles (IQR, 1-3). IDAC-treated patients showed in average a higher age (median (IQR) 58.5 (49-62) years vs. 50 (41-56) years) and more comorbidities with 43.8% having an HCT-CI score of 2-4, compared to 22.3% among HiDAC-treated patients. Alongside, significantly more secondary (5.1% vs. 3.1%) and therapy-related (12.4% vs. 4.1%) AML as well as more adverse (14.5% vs. 6.5%) and less favorable (40.6% vs. 56%) genetic risk features according to ELN 2017 risk classification were found among IDAC-treated patients. After propensity score weighting for differences in patient and disease characteristics, overall survival after 5 years was comparable between HiDAC-treated (71.1 %) and IDAC-treated (67.7%) patients. Moreover, no significant differences in relapse-free survival were observed after 5 years (47.4 vs. 45.2%). Notably, more patients treated with IDAC received allogeneic stem cell transplantation in first remission (37.6 vs. 19.8%) while significantly more HiDAC-treated patients underwent allogeneic stem cell transplantation in relapse (30.8 vs. 20.2%). Censoring for allogeneic stem cell transplantation in first remission revealed no significant survival difference with regard to cytarabine dosage. Considering only ELN favorable risk AML patients, there was no difference in 5-years overall (80.5% vs. 83.9%) nor relapse-free (57.7% vs. 56.8%) survival. Of note, significantly more patients treated with HiDAC suffered from ≥3 CTCAE infectious complications (56.7 vs. 44.1%), which was more striking in patients above 50 years of age. The rate of other ≥3 CTCAE non-hematological toxicities and secondary malignancies was comparable in both treatment groups.

Conclusion: This retrospective analysis suggests no significant benefit of high dose cytarabine compared to intermediate dosages in consolidation for AML patients under 65 years of age, independent of ELN risk group.

Disclosures: Krause: Siemens: Research Funding; Takeda: Honoraria; Pfizer: Honoraria; art-tempi: Honoraria; Kosmas: Honoraria; Gilead: Other: travel support; Abbvie: Other: travel support. Schliemann: Philogen S.p.A.: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Other: travel grants; Astellas: Consultancy; AstraZeneca: Consultancy; Boehringer-Ingelheim: Research Funding; BMS: Consultancy, Other: travel grants; Jazz Pharmaceuticals: Consultancy, Research Funding; Novartis: Consultancy; Roche: Consultancy; Pfizer: Consultancy. Haenel: Jazz: Consultancy, Honoraria; GSK: Consultancy; Bayer Vital: Honoraria; Takeda: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Amgen: Consultancy; Celgene: Consultancy, Honoraria. Brummendorf: Takepart Media: Honoraria; Repeat Diagnostics: Research Funding; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Honoraria, Patents & Royalties, Research Funding; Janssen: Honoraria; Bristol Myers: Research Funding. Fransecky: Abbvie: Honoraria, Research Funding; Medac: Honoraria; Novartis: Honoraria; Amgen: Honoraria; Takeda: Honoraria. Einsele: Janssen, Celgene/BMS, Amgen, GSK, Sanofi: Consultancy, Honoraria, Research Funding. Held: Roche: Research Funding; Amgen: Research Funding; MSD: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Acortech Biopharma: Research Funding; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Platzbecker: Janssen: Honoraria; Celgene/BMS: Honoraria; AbbVie: Honoraria; Geron: Honoraria; Takeda: Honoraria; Novartis: Honoraria. Baldus: Amgen: Honoraria; Celgene/BMS: Honoraria; Novartis: Honoraria; Jazz: Honoraria. Mueller-Tidow: Janssen Cilag: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Bioline: Consultancy, Research Funding.

*signifies non-member of ASH