Chidamide, decitabine, cytarabine, aclarubicin, and granulocyte colony-stimulating factor (CDCAG) in patients with relapsed/refractory acute myeloid leukemia: a single-arm, phase 1/2 study

Autor: Guofeng Chen, Yinghua Li, Xiao-Ning Gao, Yin Zhang, Yi-Gai Ma, Kai Sun, Sujun Gao, Zhuogang Liu, Lixin Wang, Xin Wang, Jian-Liang Shen, Hui Liu, Li Yu, Lin-Hua Yang, Wei Zhou, Xinquan Li, Xudong Wei, Mei-Yun Fang, Jianmin Luo
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Oncology
Male
medicine.medical_treatment
Aminopyridines
Gene mutation
chemistry.chemical_compound
0302 clinical medicine
Relapsed/refractory acute myeloid leukemia
Chidamide
Antineoplastic Combined Chemotherapy Protocols
Granulocyte Colony-Stimulating Factor
Genetics (clinical)
Antibiotics
Antineoplastic
Remission Induction
Cytarabine
Myeloid leukemia
Middle Aged
Granulocyte colony-stimulating factor
Leukemia
Myeloid
Acute
Treatment Outcome
030220 oncology & carcinogenesis
Benzamides
Female
Aclarubicin
medicine.drug
Adult
medicine.medical_specialty
Antimetabolites
Antineoplastic
Adolescent
Decitabine
DNA methyltransferase inhibitor
Disease-Free Survival
03 medical and health sciences
Young Adult
Internal medicine
Genetics
medicine
Humans
Molecular Biology
Chemotherapy
Histone deacetylase inhibitor
business.industry
Research
030104 developmental biology
chemistry
Next-generation sequencing
business
Developmental Biology
Zdroj: Clinical Epigenetics
ISSN: 1868-7083
1868-7075
Popis: Background Epigenetic mechanisms play an important role in the chemoresistance of acute myeloid leukemia (AML). The clinical response to epigenetic modifier-based chemotherapy in patients with relapsed/refractory AML (r/r AML) is unclear. This multicenter clinical trial evaluated the safety and efficacy of epigenetic modifiers (chidamide and decitabine) in combination with aclarubicin, cytarabine, and granulocyte colony-stimulating factor (G-CSF) in patients with r/r AML. Results Adult patients with r/r AML were treated with chidamide, decitabine, cytarabine, aclarubicin, and G-CSF (CDCAG). The primary measures were overall response (OR), overall survival (OS), and safety. Next-generation sequencing was performed to analyze the correlation between gene mutations and response. A total of 93 patients with r/r AML were enrolled. Overall, 24 patients had a complete remission (CR) and 19 patients achieved CR with incomplete blood count recovery (CRi). The overall response rate (ORR) was 46.2%. The overall survival of these 43 patients who achieved CR/CRi was significantly longer than that of patients who failed to achieve remission (563 vs 152 days, P < 0.0001). Of the patients with mutations in epigenetic and transcription factor-related genes, but without internal tandem duplications in FMS-like tyrosine kinase3 (FLT3-ITDs), 55.6% achieved CR/CRi, whereas the ORR was 28.2% for patients with mutations in other genes. Conclusions The CDCAG regimen was well tolerated and effective in r/r AML. Patients with epigenetic and transcription factor-related gene mutations, but without FLT3-ITD mutations, may benefit from this regimen. Trial registration Clinical Trials, NCT02886559. Registered 01 September 2016
Databáze: OpenAIRE
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