Intensified cytarabine dose during consolidation in adult AML patients under 65 years is not associated with survival benefit: real-world data from the German SAL-AML registry

Hanoun M, Ruhnke L, Kramer M, Hanoun C, Schaefer-Eckart K, Steffen B, Sauer T, Krause S, Schliemann C, Mikesch JH, Kaufmann M, Haenel M, Jost E, Bruemmendorf TH, Fransecky L, Kraus S, Einsele H, Niemann D, Neubauer A, Kullmer J, Seggewiss-Bernhard R, Goerner M, Held G, Kaiser U, Scholl S, Hochhaus A, Reinhardt HC, Platzbecker U, Baldus CD, Mueller-Tidow C, Bornhaeuser M, Serve H, Roellig C (2022)

Publication Type: Journal article

Publication year: 2022

Journal

DOI: 10.1007/s00432-022-04356-9

Abstract

Purpose: Higher doses of cytarabine appear to improve long-term outcome in acute myeloid leukemia (AML), in particular for younger patients. To this end, the optimal dosage of single-agent cytarabine in consolidation therapy remains elusive. Here, we assessed the impact of different dosages of cytarabine consolidation after 7 + 3 induction on outcome in a large real-world data set from the German Study Alliance Leukemia-Acute Myeloid Leukemia (SAL-AML) registry. Methods: Patients between 18 and 64 years of age, registered between April 2005 and September 2020, 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: Six-hundred-forty-two patients received HiDAC consolidation with median dosage of 17.6 (IQR (interquartile range), 16.5–18.0) g/m² for a median number of 3 cycles (IQR, 2–3), whereas 178 patients received IDAC consolidation with 5.9 (IQR, 5.7–8.6) g/m² for a median of 2 cycles (IQR, 1–3). Both groups differed significantly in some important characteristics (age, sex, cytogenetic risk group, ECOG performance status, disease status, HCT-CI, number of induction cycles). After propensity score weighting for differences in patient and disease characteristics, relapse-free survival after 2 years was comparable between HiDAC-treated (55.3%) and IDAC-treated (55.6%) patients (HR = 0.935, p = 0.69). Moreover, no significant differences in overall survival were observed after 2 years (84.7 vs. 80.6%, HR = 1.101, p = 0.65). Notably, more patients treated with IDAC received allogeneic hematopoietic cell transplantation in first remission (37.6 vs. 19.8%, p < 0.001). Censoring for allogeneic hematopoietic cell transplantation in first remission revealed no significant survival difference with regard to cytarabine dosage. Considering only of European LeukemiaNet (ELN) favorable-risk AML patients, there was no significant difference in outcome. Of note, significantly more patients treated with HiDAC suffered from ≥ 3 CTCAE infectious complications (56.7 [95%-CI 52.8–60.6%] vs. 44.1% [95%-CI 36.6–51.7%]; p = 0,004). The rate of other ≥ 3 CTCAE non-hematological toxicities and secondary malignancies was comparable in both treatment groups. Conclusions: 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. Trial registration: NCT03188874.

Authors with CRIS profile

Involved external institutions

Universitätsklinikum Frankfurt am Main (KGU) Germany (DE) Universitätsklinikum Essen Germany (DE) Technische Universität Dresden Germany (DE) Klinikum Nürnberg Germany (DE) Universitätsklinikum Heidelberg Germany (DE) Universitätsklinikum Münster Germany (DE) Robert-Bosch-Krankenhaus Germany (DE) Klinikum Chemnitz Germany (DE) Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen Germany (DE) Universitätsklinikum Schleswig-Holstein (UKSH) Germany (DE) Universitätsklinikum Würzburg Germany (DE) Gemeinschaftsklinikum Mittelrhein Germany (DE) Universitätsklinikum Gießen und Marburg (UKGM) Germany (DE) DIAKO Evangelisches Diakonie-Krankenhaus gGmbH Germany (DE) Sozialstiftung Bamberg Germany (DE) Klinikum Bielefeld Germany (DE) Universität des Saarlandes (UdS) Germany (DE) St. Bernward Krankenhaus Germany (DE) Universitätsklinikum Jena Germany (DE) Universitätsklinikum Leipzig Germany (DE)

How to cite

APA:

Hanoun, M., Ruhnke, L., Kramer, M., Hanoun, C., Schaefer-Eckart, K., Steffen, B.,... Roellig, C. (2022). Intensified cytarabine dose during consolidation in adult AML patients under 65 years is not associated with survival benefit: real-world data from the German SAL-AML registry. Journal of Cancer Research and Clinical Oncology. https://doi.org/10.1007/s00432-022-04356-9

MLA:

Hanoun, Maher, et al. "Intensified cytarabine dose during consolidation in adult AML patients under 65 years is not associated with survival benefit: real-world data from the German SAL-AML registry." Journal of Cancer Research and Clinical Oncology (2022).

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