Durable remissions with venetoclax monotherapy in secondary AML refractory to hypomethylating agents and high expression of BCL-2 and/or BIM.
Aged
Aged, 80 and over
Antineoplastic Agents
/ therapeutic use
Bcl-2-Like Protein 11
/ genetics
Biomarkers, Tumor
Bridged Bicyclo Compounds, Heterocyclic
/ therapeutic use
DNA Methylation
/ drug effects
Drug Resistance, Neoplasm
Female
Gene Expression Regulation, Leukemic
/ drug effects
Humans
Leukemia, Myeloid, Acute
/ diagnosis
Male
Proto-Oncogene Proteins c-bcl-2
/ genetics
Remission Induction
Retreatment
Sulfonamides
/ therapeutic use
Treatment Outcome
BCL-2
BIM
IDH1
IDH2
MCL-1
azacitidine
hypomethylating agents
myeloproliferative neoplasm
secondary acute myeloid leukemia
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:
May 2019
May 2019
Historique:
received:
28
01
2019
revised:
29
01
2019
accepted:
30
01
2019
pubmed:
7
2
2019
medline:
15
11
2019
entrez:
7
2
2019
Statut:
ppublish
Résumé
Acute myeloid leukemia (AML) is a disease of the elderly population and survival remains poor after failure of hypomethylating agents (HMA). The BCL-2 inhibitor venetoclax demonstrated activity as monotherapy and in combination with chemotherapy or HMA in AML. In this case series, patients with secondary AML (sAML) not eligible for intensive chemotherapy and refractory to HMA were treated with venetoclax within a named patient program at our tertiary cancer center in Salzburg, Austria. Between April 2017 and September 2018, seven patients with sAML received venetoclax therapy. Two out of seven patients achieved a complete remission upon venetoclax initiation with a PFS of 505 days and 352 days and another patient achieved complete peripheral blood blast clearing within nine days after start of venetoclax. Among the venetoclax responders, primary refractory disease to prior HMA therapy was documented, 2 patients harbored IDH1/IDH2 mutations and one patient had an antecedent myeloproliferative neoplasm. High BCL-2 and/or BIM expression in myeloblasts was found in venetoclax responders and response was significantly associated with overall survival (responders: 364 days versus non-responders: 24 days, P = 0.018). Venetoclax monotherapy is safe and is able to induce durable responses in elderly patients with secondary AML after treatment failure with HMA.
Identifiants
pubmed: 30725494
doi: 10.1111/ejh.13218
pmc: PMC6849823
doi:
Substances chimiques
Antineoplastic Agents
0
BCL2 protein, human
0
Bcl-2-Like Protein 11
0
Biomarkers, Tumor
0
Bridged Bicyclo Compounds, Heterocyclic
0
Proto-Oncogene Proteins c-bcl-2
0
Sulfonamides
0
venetoclax
N54AIC43PW
Types de publication
Case Reports
Langues
eng
Sous-ensembles de citation
IM
Pagination
437-441Subventions
Organisme : Austrian Science Fund FWF
ID : I 3282
Pays : Austria
Informations de copyright
© 2019 The Authors. European Journal of Haematology Published by John Wiley & Sons Ltd.
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