Venetoclax-based non-intensive induction followed by allogenic stem-cell transplantation in elderly acute myeloid leukemia patients with adverse cytogenetics.
TP53
acute myeloid leukemia
adverse cytogenetics
venetoclax
Journal
European journal of haematology
ISSN: 1600-0609
Titre abrégé: Eur J Haematol
Pays: England
ID NLM: 8703985
Informations de publication
Date de publication:
11 Aug 2024
11 Aug 2024
Historique:
revised:
21
07
2024
received:
03
04
2024
accepted:
25
07
2024
medline:
12
8
2024
pubmed:
12
8
2024
entrez:
12
8
2024
Statut:
aheadofprint
Résumé
Elderly acute myeloid leukemia (AML) patients with poor-risk cytogenetics have a poor outcome with intensive chemotherapy (IC). While Venetoclax (VEN) has changed the outcomes of elderly unfit patients treatment, it is unknown whether it could be effective in poor-risk cytogenetics 60-75 years old patients. We included 60-75-year-old AML patients eligible to allogenic stem cell transplantation (allo-SCT) treated with VEN (combined with azacitidine or with Cladribin and Aracytine) at Institut Paoli Calmettes, between 2020 and 2023 and compared this cohort with patients treated by IC between 2010 and 2019. Twenty six patients were treated with VEN (17 in combination with azacitidine and 9 with Cladribin and Aracytine) and 90 were treated with IC. Thirteen patients (50%) had a TP53 mutation. The median time for leucocyte and platelet counts recovery was 26 days (range 0-103) and 26 days (range, 0-63). The median duration of the first hospitalization was 32 days (ranges, 7-79). The composite response rate was 69% (CR = 50%, CRi = 4%, MLFS = 15%). Allo-SCT could be performed in 42% of cases. Median overall survival (OS) was 7.9 months (20.9 months in the group of patients who transitioned to allo-SCT). We found no difference with the historical cohort of patients treated with IC except a trend toward less lower and upper tract gastro-intestinal (GI) tract infections in the VEN group (respectively 8% vs 26%, p = .06; and 0% vs. 13% p = .06). VEN-based treatment was found to be effective in high risk AML can be considered as an alternative to IC in patients aged 60-75 with adverse cytogenetics.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2024 The Author(s). European Journal of Haematology published by John Wiley & Sons Ltd.
Références
Howlader N, Noone AM, Krapcho M, et al., eds. SEER Cancer Statistics Review, 1975–2016. National Cancer Institute; 2019.
Appelbaum FR, Gundacker H, Head DR, et al. Age and acute myeloid leukemia. Blood. 2006;107(9):3481‐3485.
Döhner H, Weisdorf DJ, Bloomfield CD. Acute myeloid leukemia. N Engl J Med. 2015;373(12):1136‐1152.
Bullinger L, Döhner K, Döhner H. Genomics of acute myeloid leukemia diagnosis and pathways. J Clin Oncol. 2017;35(9):934‐946.
Papaemmanuil E, Gerstung M, Bullinger L, et al. Genomic classification and prognosis in acute myeloid leukemia. N Engl J Med. 2016;374(23):2209‐2221.
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.
Patel JP, Gönen M, Figueroa ME, et al. Prognostic relevance of integrated genetic profiling in acute myeloid leukemia. N Engl J Med. 2012;366(12):1079‐1089.
Döhner H, Estey E, Grimwade D, et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017;129(4):424‐447.
Schlenk RF, Döhner K, Mack S, et al. Prospective evaluation of allogeneic hematopoietic stem‐cell transplantation from matched related and matched unrelated donors in younger adults with high‐risk acute myeloid leukemia: German‐Austrian trial AMLHD98A. J Clin Oncol. 2010;28(30):4642‐4648.
Slovak ML, Kopecky KJ, Cassileth PA, et al. Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: a southwest oncology group/eastern cooperative oncology group study. Blood. 2000;96(13):4075‐4083.
Burnett AK, Wheatley K, Goldstone AH, et al. The value of allogeneic bone marrow transplant in patients with acute myeloid leukaemia at differing risk of relapse: results of the UK MRC AML 10 trial. Br J Haematol. 2002;118(2):385‐400.
Cornelissen JJ, Gratwohl A, Schlenk RF, et al. The European LeukemiaNet AML working party consensus statement on allogeneic HSCT for patients with AML in remission: an integrated‐risk adapted approach. Nat Rev Clin Oncol. 2012;9(10):579‐590.
Prassek VV, Rothenberg‐Thurley M, Sauerland MC, et al. Genetics of acute myeloid leukemia in the elderly: mutation spectrum and clinical impact in intensively treated patients aged 75 years or older. Haematologica. 2018;103(11):1853‐1861.
Juliusson G, Antunovic P, Derolf A, et al. Age and acute myeloid leukemia: real world data on decision to treat and outcomes from the Swedish acute leukemia registry. Blood. 2009;113(18):4179‐4187.
Harbi S, Brac de la Perriere L, Bouchacourt B, et al. Peripheral blood haploidentical hematopoietic cell transplantation for patients aged 70 years and over with acute myeloid leukemia or high‐risk myelodysplastic syndrome. Bone Marrow Transplant. 2024;59(1):101‐106.
Devillier R, Forcade E, Garnier A, et al. In‐depth time‐dependent analysis of the benefit of allo‐HSCT for elderly patients with CR1 AML: a FILO study. Blood Adv. 2022;6(6):1804‐1812.
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.
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.
Cherry EM, Abbott D, Amaya M, et al. Venetoclax and azacitidine compared with induction chemotherapy for newly diagnosed patients with acute myeloid leukemia. Blood Adv. 2021;5(24):5565‐5573.
Matthews AH, Perl AE, Luger SM, et al. Real‐world effectiveness of CPX‐351 vs venetoclax and azacitidine in acute myeloid leukemia. Blood Adv. 2022;6(13):3997‐4005.
Kadia TM, Reville PK, Wang X, et al. Phase II study of Venetoclax added to Cladribine plus low‐dose Cytarabine alternating with 5‐Azacitidine in older patients with newly diagnosed acute myeloid leukemia. J Clin Oncol. 2022;40(33):3848‐3857.
Sorror ML, Storer BE, Fathi AT, et al. Development and validation of a novel acute myeloid leukemia‐composite model to estimate risks of mortality. JAMA Oncol. 2017;3(12):1675‐1682.
Hourmant Y, Kouatchet A, López R, et al. Impact of early ICU admission for critically ill cancer patients: post‐hoc analysis of a prospective multicenter multinational dataset. J Crit Care. 2021;62:6‐11.
Garciaz S, Hospital M‐A, Collette Y, Vey N. Venetoclax resistance in acute myeloid leukemia. Cancer. 2024;16:1091. doi:10.3390/cancers16061091