Female and preserved platelet count subgroups of myelodysplastic syndrome patients benefit from standard-dose azacitidine.
azacitidine
dose
myelodysplastic syndrome
platelet counts
sex
Journal
Cancer reports (Hoboken, N.J.)
ISSN: 2573-8348
Titre abrégé: Cancer Rep (Hoboken)
Pays: United States
ID NLM: 101747728
Informations de publication
Date de publication:
28 Nov 2023
28 Nov 2023
Historique:
revised:
12
10
2023
received:
05
07
2023
accepted:
12
11
2023
medline:
28
11
2023
pubmed:
28
11
2023
entrez:
28
11
2023
Statut:
aheadofprint
Résumé
Hypomethylating agents, including azacytidine (AZA), are standard therapeutics for patients with high-risk myelodysplastic syndromes (MDS), a group of myeloid neoplasms. However, treatment schedules are not unified in real-world practice; in addition to the standard 7-day (standard-dose) schedule, shortened (reduced-dose) schedules are also used. The aim of this study was to discover the patient group(s) which show differential efficacy between standard-and reduced-dose AZA to MDS. The outcome of different AZA doses in a cohort of 151 MDS patients were retrospectively analyzed. Overall survival (OS) was not significantly different between standard- and reduced-dose AZA groups by multivariate analysis. However, an interaction was found between either the sex (female vs. male), the platelet counts (< 40 × 10 We identified the union of female and preserved platelet count subgroups which benefited from standard-dose AZA, imparting crucial information to physicians planning treatment regimens in MDS patients.
Sections du résumé
BACKGROUND
BACKGROUND
Hypomethylating agents, including azacytidine (AZA), are standard therapeutics for patients with high-risk myelodysplastic syndromes (MDS), a group of myeloid neoplasms. However, treatment schedules are not unified in real-world practice; in addition to the standard 7-day (standard-dose) schedule, shortened (reduced-dose) schedules are also used.
AIMS
OBJECTIVE
The aim of this study was to discover the patient group(s) which show differential efficacy between standard-and reduced-dose AZA to MDS.
METHODS AND RESULTS
RESULTS
The outcome of different AZA doses in a cohort of 151 MDS patients were retrospectively analyzed. Overall survival (OS) was not significantly different between standard- and reduced-dose AZA groups by multivariate analysis. However, an interaction was found between either the sex (female vs. male), the platelet counts (< 40 × 10
CONCLUSION
CONCLUSIONS
We identified the union of female and preserved platelet count subgroups which benefited from standard-dose AZA, imparting crucial information to physicians planning treatment regimens in MDS patients.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1938Subventions
Organisme : Japan Agency for Medical Research and Development
ID : cm0106505h
Organisme : Japan Society for the Promotion of Science
ID : 21K16261
Informations de copyright
© 2023 The Authors. Cancer Reports published by Wiley Periodicals LLC.
Références
Swerdlow SH, Campo E, Harris NL, et al. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, WHO Classification of Tumours. Vol 2. 4th ed. International Agency for Research on Cancer; 2017.
Cazzola M. Myelodysplastic syndromes. N Engl J Med. 2020;383(14):1358-1374.
Kantarjian H, Issa JP, Rosenfeld CS, et al. Decitabine improves patient outcomes in myelodysplastic syndromes: results of a phase III randomized study. Cancer. 2006;106(8):1794-1803.
Silverman LR, Demakos EP, Peterson BL, et al. Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the cancer and leukemia group B. J Clin Oncol. 2002;20(10):2429-2440.
Fenaux P, Mufti GJ, Hellstrom-Lindberg E, et al. Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol. 2009;10(3):223-232.
Palacios-Berraquero ML, Alfonso-Piérola A. Current therapy of the patients with MDS: walking towards personalized therapy. J Clin Med. 2021;10(10).
Lyons RM, Cosgriff TM, Modi SS, et al. Hematologic response to three alternative dosing schedules of azacitidine in patients with myelodysplastic syndromes. J Clin Oncol. 2009;27(11):1850-1856.
Laribi K, Bolle D, Alani M, et al. Impact of the relative dose intensity on survival of patients with high-risk myelodysplastic syndromes treated with Azacitidine. Cancer Med. 2019;8(5):2188-2195.
Martin MG, Walgren RA, Procknow E, et al. A phase II study of 5-day intravenous azacitidine in patients with myelodysplastic syndromes. Am J Hematol. 2009;84(9):560-564.
Fujimaki K, Miyashita K, Kawasaki R, Tomita N. Efficacy and safety of a 5-day regimen of azacitidine for patients with high-risk myelodysplastic syndromes. Eur J Haematol. 2016;97(3):228-231.
García-Delgado R, de Miguel D, Bailén A, et al. Effectiveness and safety of different azacitidine dosage regimens in patients with myelodysplastic syndromes or acute myeloid leukemia. Leuk Res. 2014;38(7):744-750.
Grinblatt DL, Sekeres MA, Komrokji RS, Swern AS, Sullivan KA, Narang M. Patients with myelodysplastic syndromes treated with azacitidine in clinical practice: the AVIDA registry. Leuk Lymphoma. 2015;56(4):887-895.
DiNardo CD, Jonas BA, Pullarkat V, et al. Azacitidine and Venetoclax in previously untreated acute myeloid leukemia. N Engl J Med. 2020;383(7):617-629.
Sallman DA, Al Malki MM, Asch AS, et al. Magrolimab in combination with Azacitidine in patients with higher-risk myelodysplastic syndromes: final results of a phase Ib study. J Clin Oncol. 2023;41(15):2815-2826.
Cluzeau T, Sebert M, Rahmé R, et al. Eprenetapopt plus Azacitidine in TP53-mutated myelodysplastic syndromes and acute myeloid leukemia: a phase II study by the Groupe francophone des Myélodysplasies (GFM). J Clin Oncol. 2021;39(14):1575-1583.
Sallman DA, DeZern AE, Garcia-Manero G, et al. Eprenetapopt (APR-246) and Azacitidine in TP53-mutant myelodysplastic syndromes. J Clin Oncol. 2021;39(14):1584-1594.
Garcia-Manero G, Goldberg AD, Winer ES, et al. Eprenetapopt combined with venetoclax and azacitidine in TP53-mutated acute myeloid leukaemia: a phase 1, dose-finding and expansion study. Lancet Haematol. 2023;10(4):e272-e283.
Miyazaki Y, Kiguchi T, Sato S, et al. Prospective comparison of 5- and 7-day administration of azacitidine for myelodysplastic syndromes: a JALSG MDS212 trial. Int J Hematol. 2022;116:228-238.
Bennett JM, Catovsky D, Daniel MT, et al. Proposals for the classification of the myelodysplastic syndromes. Br J Haematol. 1982;51(2):189-199.
Silverman LR, McKenzie DR, Peterson BL, et al. Further analysis of trials with azacitidine in patients with myelodysplastic syndrome: studies 8421, 8921, and 9221 by the cancer and leukemia group B. J Clin Oncol. 2006;24(24):3895-3903.
Santini V, Ossenkoppele GJ. Hypomethylating agents in the treatment of acute myeloid leukemia: a guide to optimal use. Crit Rev Oncol Hematol. 2019;140:1-7.
Platzbecker U, Fenaux P, Adès L, et al. Proposals for revised IWG 2018 hematological response criteria in patients with MDS included in clinical trials. Blood. 2019;133(10):1020-1030.
Greenberg PL, Tuechler H, Schanz J, et al. Revised international prognostic scoring system for myelodysplastic syndromes. Blood. 2012;120(12):2454-2465.
Kanda Y. Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant. 2013;48(3):452-458.
Itzykson R, Thépot S, Quesnel B, et al. Prognostic factors for response and overall survival in 282 patients with higher-risk myelodysplastic syndromes treated with azacitidine. Blood. 2011;117(2):403-411.
Mahfouz RZ, Jankowska A, Ebrahem Q, et al. Increased CDA expression/activity in males contributes to decreased cytidine analog half-life and likely contributes to worse outcomes with 5-azacytidine or decitabine therapy. Clin Cancer Res. 2013;19(4):938-948.
Fleming RA, Capizzi RL, Rosner GL, et al. Clinical pharmacology of cytarabine in patients with acute myeloid leukemia: a cancer and leukemia group B study. Cancer Chemother Pharmacol. 1995;36(5):425-430.