Phase 2 study of epigenetic priming with decitabine followed by cytarabine for acute myeloid leukemia in older patients.


Journal

American journal of hematology
ISSN: 1096-8652
Titre abrégé: Am J Hematol
Pays: United States
ID NLM: 7610369

Informations de publication

Date de publication:
22 Jan 2024
Historique:
revised: 08 12 2023
received: 24 08 2023
accepted: 15 12 2023
medline: 23 1 2024
pubmed: 23 1 2024
entrez: 23 1 2024
Statut: aheadofprint

Résumé

Acute myeloid leukemia (AML) in older patients has a poor prognosis, low complete remission (CR) rates, and poor overall survival (OS). Preclinical studies have shown synergistic effects of epigenetic priming with hypomethylating agents followed by cytarabine. Based on these data, we hypothesized that an induction regimen using epigenetic priming with decitabine, followed by cytarabine would be effective and safe in older patients with previously untreated AML. Here, we conducted a phase 2 trial in which older patients with previously untreated AML received an induction regimen consisting of 1 or 2 courses of decitabine 20 mg/m

Identifiants

pubmed: 38258329
doi: 10.1002/ajh.27212
doi:

Banques de données

ClinicalTrials.gov
['NCT01829503']

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : Hillman Cancer Center, Medical Center, University of Pittsburgh
ID : P30 CA047904-24

Informations de copyright

© 2024 Wiley Periodicals LLC.

Références

Sekeres MA, Guyatt G, Abel G, et al. American Society of Hematology 2020 guidelines for treating newly diagnosed acute myeloid leukemia in older adults. Blood Adv. 2020;4(15):3528-3549. doi:10.1182/bloodadvances.2020001920
Dohner H, Weisdorf DJ, Bloomfield CD. Acute myeloid leukemia. N Engl J Med. 2015;373(12):1136-1152. doi:10.1056/NEJMra1406184
Short NJ, Rytting ME, Cortes JE. Acute myeloid leukaemia. Lancet. 2018;392(10147):593-606. doi:10.1016/S0140-6736(18)31041-9
Plass C, Oakes C, Blum W, Marcucci G. Epigenetics in acute myeloid leukemia. Semin Oncol. 2008;35(4):378-387. doi:10.1053/j.seminoncol.2008.04.008
Bullinger L, Ehrich M, Dohner K, et al. Quantitative DNA methylation predicts survival in adult acute myeloid leukemia. Blood. 2010;115(3):636-642. doi:10.1182/blood-2009-03-211003
Agrawal S, Unterberg M, Koschmieder S, et al. DNA methylation of tumor suppressor genes in clinical remission predicts the relapse risk in acute myeloid leukemia. Cancer Res. 2007;67(3):1370-1377. doi:10.1158/0008-5472.CAN-06-1681
Kroeger H, Jelinek J, Estecio MR, et al. Aberrant CpG Island methylation in acute myeloid leukemia is accentuated at relapse. Blood. 2008;112(4):1366-1373. doi:10.1182/blood-2007-11-126227
Derissen EJ, Beijnen JH, Schellens JH. Concise drug review: azacitidine and decitabine. Oncologist. 2013;18(5):619-624. doi:10.1634/theoncologist.2012-0465
Cashen AF, Schiller GJ, O'Donnell MR, DiPersio JF. Multicenter, phase II study of decitabine for the first-line treatment of older patients with acute myeloid leukemia. J Clin Oncol. 2010;28(4):556-561. doi:10.1200/JCO.2009.23.9178
Kantarjian HM, Thomas XG, Dmoszynska A, et al. Multicenter, randomized, open-label, phase III trial of decitabine versus patient choice, with physician advice, of either supportive care or low-dose cytarabine for the treatment of older patients with newly diagnosed acute myeloid leukemia. J Clin Oncol. 2012;30(21):2670-2677. doi:10.1200/JCO.2011.38.9429
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. doi:10.1056/NEJMoa2012971
Montesinos P, Recher C, Vives S, et al. Ivosidenib and azacitidine in IDH1-mutated acute myeloid leukemia. N Engl J Med. 2022;386(16):1519-1531. doi:10.1056/NEJMoa2117344
Qin T, Youssef EM, Jelinek J, et al. Effect of cytarabine and decitabine in combination in human leukemic cell lines. Clin Cancer Res. 2007;13(14):4225-4232. doi:10.1158/1078-0432.CCR-06-2762
Avramis VI, Powell WC, Mecum RA. Cellular metabolism of 1-beta-D-arabinofuranosyl-5-azacytosine and incorporation into DNA and RNA of human lymphoid CEM/0 and CEM/dCk(−) cells. Cancer Chemother Pharmacol. 1989;25(1):19-24. doi:10.1007/BF00694333
Borthakur G, Huang X, Kantarjian H, et al. Report of a phase 1/2 study of a combination of azacitidine and cytarabine in acute myelogenous leukemia and high-risk myelodysplastic syndromes. Leuk Lymphoma. 2010;51(1):73-78. doi:10.3109/10428190903318329
Scandura JM, Roboz GJ, Moh M, et al. Phase 1 study of epigenetic priming with decitabine prior to standard induction chemotherapy for patients with AML. Blood. 2011;118(6):1472-1480. doi:10.1182/blood-2010-11-320093
Cheson BD, Bennett JM, Kopecky KJ, et al. Revised recommendations of the International Working Group for Diagnosis, standardization of response criteria, treatment outcomes, and reporting standards for therapeutic trials in acute myeloid leukemia. J Clin Oncol. 2003;21(24):4642-4649. doi:10.1200/JCO.2003.04.036
Dohner H, Estey EH, Amadori S, et al. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood. 2010;115(3):453-474. doi:10.1182/blood-2009-07-235358
Cella D, Jensen SE, Webster K, et al. Measuring health-related quality of life in leukemia: the Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu) questionnaire. Value Health. 2012;15(8):1051-1058. doi:10.1016/j.jval.2012.08.2210
Grimwade D, Hills RK, Moorman AV, et al. Refinement of cytogenetic classification in acute myeloid leukemia: determination of prognostic significance of rare recurring chromosomal abnormalities among 5876 younger adult patients treated in the United Kingdom Medical Research Council trials. Blood. 2010;116(3):354-365. doi:10.1182/blood-2009-11-254441
Friedman J, Tibshirani R, Hastie T. Regularization paths for generalized linear models via coordinate descent. J Stat Softw. 2010;33(1):1-22. https://cran.r-project.org/web/packages/glmnet/citation.html
Wei AH, Panayiotidis P, Montesinos P, et al. Long-term follow-up of VIALE-C in patients with untreated AML ineligible for intensive chemotherapy. Blood. 2022;140(25):2754-2756. doi:10.1182/blood.2022016963
Welch JS, Petti AA, Miller CA, et al. TP53 and Decitabine in acute myeloid leukemia and myelodysplastic syndromes. N Engl J Med. 2016;375(21):2023-2036. doi:10.1056/NEJMoa1605949
Pollyea DA, Pratz KW, Wei AH, et al. Outcomes in patients with poor-risk cytogenetics with or without TP53 mutations treated with Venetoclax and Azacitidine. Clin Cancer Res. 2022;28(24):5272-5279. doi:10.1158/1078-0432.CCR-22-1183

Auteurs

Annie Im (A)

UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, USA.

Kevin Quann (K)

UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, USA.

Mounzer Agha (M)

UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, USA.

Anastasios Raptis (A)

UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, USA.

Robert L Redner (RL)

UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, USA.

Jing-Zhou Hou (JZ)

UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, USA.

Rafic Farah (R)

UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, USA.

Kathleen A Dorritie (KA)

UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, USA.

Alison R Sehgal (AR)

UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, USA.

Daniel Normolle (D)

Department of Biostatistics, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

Dana H Bovbjerg (DH)

UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, USA.

Nidhi Aggarwal (N)

Department of Pathology, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania, USA.

James Herman (J)

UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, USA.

Konstantinos Lontos (K)

UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, USA.

Michael Boyiadzis (M)

UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, USA.

Classifications MeSH